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QP971  .K23  1909     The  harmful  effects 


RECAP 


Kebler 

...The  harmful  effects  of  acetanilid,  antipyrin 
and  Dhenacetin. 


QP971    K23    1909 


THE  LIBRARIES 


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http://www.archive.org/details/harmfuleffectsofOOkebl 


Issued  July  :i,  l<jij<j. 


U.  S.  DEPARTMENT  OF  AGRICULTURE, 

BUREAU  OF  CHEMISTRY— BULLETIN  No.  126. 

II    W    WILEY,  Chief  of  Bureau. 


THE  HARMFUL  EFFECTS  OF  ACETANILID, 
ANTIPYRIN,  AND  PHENACETIN. 


By 


L.  F.  KEBLER,  Ph.  C,  M.  D., 

Chief,  Division  of  Drugs, 

WITH   THE   COLLABORATION'    OF 

Drs.  F.  p.  morgan  and  PHILIP  RUPP, 

Assistant  Chemists. 


WASHINGTON: 

GOVERNMENT    PRINTING    OFFICE. 

1  0  0  9 . 


ORGANIZATION  OF  BUEEAU  OF  CHEMISTRY. 

H.  W.  Wiley,  Chemist  and  Chief  of  Bureau, 
F.  L.  DuPTLAP,  Associate  Chemist. 
W.  D.  BiGELOW,  Assistant  Chief  of  Bureau. 
F.  B.  LiKTON,  Chief  Clerk. 
A.  L.  Pierce,  Editorial  Clerk. 
M.  W.  Taylor,  Liltrarian. 
Division  of  Foods,  W.  D.  Bigelow,  Chief.  - 

Food  Inspection  Laboratory,  L.  M.  Tolman,  Chief. 

Food  Technology  Laboratory,  E.  M.  Chace,  Chief  and  Assistant  Chief  ({ 
Division . 

Oil,  Fat,  and  Wax  Laboratory.     [Not  appointed.] 
Division  of  Drugs,  L.  F.  Kebler,  Chief. 

Drug  Inspection  Laboratory,  G.  W.  Hoover,  C/iie/. 

Synthetic  Products  Laboratory,  W.  O.  Emery,  (77iie/. 

Essential  Oils  Laboratory.     [Not  appointed.]    . 

Pharmacological  Laboratory,  Wm.  Salant,  Acting. 
Chief  Food  and  Drug  Inspector,  W.  G.  Campbell. 
Miscellaneous  Division,  J.  K.  Haywood,  Chief. 

Water  Laboratory,  W.  W.  Skinner,  Chief. 

Cattle-Food  and  Grain  Laboratory,  J.  S.  Chamberlain,  Chief. 

Insecticide  and  Fungicide  Laboratory,  C.  C.  McDonnell,  Chief. 

Trade  Wastes  Laboratory,  under  Chief  of  Division. 
Contracts  Laboratory,  P.  H.  Walker,  Chief. 
Dairy  Laboratory,  G.  E.  Patrick,  Chief. 
Food  Research  Laboratory,  M.  E.  Pennington,  Chief. 
Leather  and  Paper  Laboratory,  F.  P.  Veitch,  Chief. 
Microchemical  Laboratory,  B.  J.  Howard,  Chief. 
Sugar  Laboratory,  A.  H.  Bryan,  Acting. 
Nitrogen  Section,  T.  C.  Trescot,  in  Charge. 
Special  Investigations: 

Physiological  Chemistry  (Animal),  F.  C.  Weber,  in  Charge. 

Physiological  Chemistry  (Vegetable),  J.  A.  Le  Cleec,  in  Charge. 

Bacteriological  Chemistry,  G.  W.  Stiles,  in  Charge. 

Enological  Chemistry,  W.  B.  Alwood,  in  Charge. 
Food  and  Drug  Inspection  Laboratories: 

Boston,  B,  H.  Smith,  Chief. 

Buffalo,  W.  L.  Dubois,  Acting. 

Chicago,  A.  L.  Winton,  Chief. 

Cincinnati,  B.  R.  Hart,  Actinpr^ 

Denver,  A,  E.  Leach,  Chief. 

Detroit,  H.  L.  Schtjlz,  Acting. 

Galveston,  T.  F.  Pappe,  Acting. 

Honolulu,  Hawaiian  Islands,  R.  A.  Dzjncan,  Acting. 

Kansas  City,  Mo.,  A.  V.  H.  Mory,  Acting. 

Nashville.     [Not  appointed.] 

New  Orleans,  C.  W.  Harrison,  Chief. 

New  York,  R.  E.  Doolittle,  Chief.  -^ 

Omaha,  S.  H.  Ross,  Ac^ingr. 

Philadelphia,  C.  S.  Brinton,  Chief. 

Pittsburg,  M.  C.  Albrech,  Acting. 

Portland,  Oreg.,  A.  L.  Knisely,  Acting. 

St.  Louis,  D.  B.  Bisbee,  Acting. 

St.  Paul,  A.  S.  Mitchell,  Chief. 

San  Francisco,  R.  A.  Gould,  Chief. 

Savannah,  W.  C.  Burnet,  Ac/inf/. 

Seattle,  H.  M.  'Loomis,  Acting. 


Issued  .Tulv  ."..  1009. 


U.  S.  DEPARTMENT  OF  AGRICULTURE, 

BUREAU  OF  CHEMISTRY— BULLETIN  No.  126. 

II.  \y.  WILKY,  Chief  of  Bureau. 


THE  HARMFUL  EFFECTS  OF  ACETAMLID, 
ANTIPYRIN,  AND  PHENACETIN. 


By 

L.  F.  KEBLER,  Ph.  C,  M.  D., 

Chief,  Division  of  Drugs, 

WITH    THK    COLLABORATION    OF 

Drs.  F.  p.  morgan  and  PHILIP  RUPP, 

Assistant  Cfiemisls. 


WASHINGTON: 

OOVKKNMKNT     I'KINTINO     OFFICE. 

10  0  0. 


LEHER  OF  TRANSMITTAL 


U.  S.  Department  of  Agriculture, 

Bureau  of  Chemistry, 
Washington,  D.  C,  February  6,  1909. 
Sir  :  I  have  the  honor  to  submit  for  your  inspection  and  approval 
a  report  containing  the  results  of  inquiries  made  by  the  Division  of 
Drugs  in  order  to  obtain  reliable  information  in  regard  to  the  harm- 
ful effects  of  acetanilid,  antipyrin,  and  phenacetin.     The  investiga- 
tion was  undertaken  at  this  time  because  the  attention  of  the  Bureau 
of  Chemistry  has  been  drawn  to  the  subject  in  connection  with  the 
labeling  in  accordance  Avith  the  food  and  drugs  act,  of  drug  products 
containing  one  or  more  of  these  agents.     I  recommend  that  this  re- 
port be  published  as  Bulletin  126  of  the  Bureau  of  Chemistry. 
Eespectfully, 

H.  W.Wiley, 

Chief  of  Bureau. 
Hon.  James  Wilson, 

Secretary  of  Agriculture. 


s 


CONTENTS. 


Page. 

Summary  of  data  collected 5 

Reports  of  jihysicians  with  regard  to  personal  experience  in  the  use  of  acet- 

anilid,  antipyrin,  and  acetphenetidin  (i)henacetin) 9 

An  incpiiry  regarding  the  importance  of  ill  effects  of  these  agents,  conducted 

])y  the  British  Medical  Association 20 

Literature  on  poisoning  by  acetanilid,  antipyrin,  and  acetphenetidin  (phe- 

nacetin) 21 

Acetanilid 21 

Introductory  resume 21 

Abstracts  of  acetanilid  cases 25 

Antipyrin 46 

Introductory  resume 46 

Abstracts  of  antipyrin  cases 47 

Acetphenetidin  ( phenacetin ) 79 

Introductory  resume 79 

Abstracts  of  acetphenetidin  ( phenacetin )  cases 80 

3 


THE  HARMFUL  EFFECTS  OF  ACETANILID,  ANTIPYRIN,  AND 

PHENACETIN. 


SUMMARY  OF  DATA  COLLECTED. 

Acetanilid,  antiijyrin,  and  acetphenetidin  (phenacetin)  were  intro- 
duced as  remedial  agents  in  1886,  1884,  and  1887,  respectively.  They 
were  at  first  used  almost  exclusively  for  the  reduction  of  the  body 
temperature  in  the  febrile  diseases,  but  as  time  went  on  they  were 
employed  less  and  less  for  this  purpose,  particularly  in  asthenic  cases, 
because  of  their  depressing  effects.  On  account  of  their  analgesic 
prof)erties,  however,  they  gradually  came  into  use  more  and  more 
for  the  relief  of  pain,  and  at  the  present  time  this  may  be  said  to 
constitute  their  most  important  field  of  usefulness.  At  the  time 
when  the}'^  were  employed  principally  as  antipyretics  their  use  was 
directed  by  the  physician,  and  they  were  administered  with  medical 
skill  and  judgment.  In  time,  however,  these  agents  became  better 
known  as  analgesics  and  were  used  more  and  more  by  the  public  at 
large,  without  medical  supervision,  for  the  relief  of  headache  and 
other  minor  aches  and  pains,  and  at  the  present  time  they  are  used  ex- 
tensively in  this  way,  largely  in  the  form  of  proprietary  preparations. 
The  indiscriminate  and  often  ill-advised  use  of  these  drugs  by  the  laity 
has  been  productive  of  l)ad  effects  in  many  instances.  Furthermore, 
the  number  of  reported  cases  of  poisoning  by  these  agents  or  prepara- 
tions containing  them  has  increased  notably  during  the  last  few  years. 

Since  the  passage  of  the  food  and  drugs  act,  June  30,  1906,  the 
attention  of  the  Department  of  Agriculture  has  been  directed  to  this 
subject,  particularly  in  connection  with  the  branding  of  drug  prod- 
ucts containing  one  or  inoi-e  of  these  agents,  aiul  an  attempt  has  been 
made  to  obtain  full  and  reliable  information  in  regard  to  their 
poisonous  qualities.  That  there  is  considerable  diversity  of  opinion 
on  this  subject  is  evident  from  the  testimony  giv^en  by  the  medical 
e.xperts  in  the  recent  case  of  the  United  States  v.  R.  N.  Harper.  Mr. 
Harper  was  the  proprietor  of  a  remedy  known  as  "Harper's  Cufor- 
hedake  Brane-Fude,"  which  contained  among  other  ingredients  acet- 
anilid and  antipyrin.  At  this  trial  one  of  the  physicians  testified 
tliat  whereas  he  had  formerly  used  acetanilid  rather  freely  he  now 
prescrilx;d  it  very  guardedly,  because  of  the  unexpected  and  untoward 
effects  which  had  been  found  to  follow  its  use.  Anolhei-  expert 
testified  that  whereas  he  had  formerly  used  it  in  his  i)rar'tic('  lie  did 


6  ACETANILID,   ANTIPYEIN,   AND   PHENACETIN. 

not  use  it  now,  because  in  his  experience  it  had  proven  uncertain  in 
effect  and  untrustworthy.  Still  another  said  he  did  not  use  it  at  all, 
and  when  asked  why,  said,  "I  am  afraid  of  it."  But  a  fourth 
physician  stated  that  he  employed  it  to  good  advantage,  and  that 
though  he  often  noted  "  bluing  of  the  skin,"  or  cyanosis,  he  regarded 
this  symptom  merely  as  a  "  signal "  or  warning  as  to  the  further 
administration  of  the  drug. 

Recent  investigation  indicates  that  all  three  of  these  drugs  are 
now  used  less  than  formerly  by  medical  practitioners.  Of  the  phy- 
sicians who  gave  information  on  this  subject  in  reply  to  an  inquirj^  by 
the  Department  of  Agriculture,  66  per  cent  state  that  they  use 
acetanilid  less  frequently  than  formerly,  nearly  66  per  cent  made  the 
same  statement  with  regard  to  antipyrin,  and  51.2  per  cent  with  re- 
gard to  phenacetin.  The  reason  given  referred  in  almost  every  in- 
stance to  the  toxic  properties  of  these  agents,  particularly  their  de- 
pressing effect  upon  the  heart.  The  fact  that  they  are  poisons  in  the 
true  sense  of  the  word  is  recognized  by  members  of  the  medical  pro- 
fession, but  it  is  doubtful  whether  the  general  public  is  aware  either 
of  this  fact  or  that  they  possess  any  possibilities  for  harm  whatever. 
Certainly  there  is  nothing  to  indicate  an  appreciation  of  these  qual- 
ities on  the  part  of  the  laity  if  one  can  judge  from  the  ever-increasing 
sale  to  the  public  of  these  drugs  and  preparations  containing  them. 
It  therefore  appears  that  the  people  in  general  should  be  informed  of 
their  poisonous  properties  and  of  the  injurious  effects  which  may 
follow  their  ill-advised,  prolonged,  or  habitual  use.  To  this  end, 
the  Department  has  recently  instituted  an  investigation  to  determine 
as  far  as  possible  the  status  of  acetanilid,  antipyrin,  and  phenacetin 
as  toxic  agents.  The  investigation  was  conducted  along  two  lines: 
First,  an  inquiry  addressed  to  medical  practitioners  in  the  United 
States  with  regard  to  their  personal  experience  with  these  drugs ;  and 
second,  a  study  of  the  cases  of  poisoning  recorded  in  medical  litera- 
ture. The  results  of  this  investigation  are  set  forth  in  the  following 
pages. 

The  purpose  of  the  inquiry  was  not  to  depreciate  in  any  way  the 
value  of  these  substances  as  medicinal  agents,  but  rather  to  furnish 
information  to  the  public  which  would  enable  them  to  understand 
that  these  remedies  should  be  employed  with  caution  in  the  absence  of 
reliable  medical  advice,  as  can  readily  be  seen  from  the  following 
correspondence  which  passed  between  the  Department  and  one  of  the 
physicians  who  furnished  information  in  reply  to  inquiries  with 
regard  to  his  personal  experience  with  these  drugs : 

I  liave  been  using  acetanilid  now  nearly  eleven  years,  observing  the  following 
rules  without  any  but  the  desired  results,  either  immediate  or  remote,  as  far 
as  my  observation  goes. 

Never  give  more  than  2.50  grains  at  a  dose. 


SUMMARY    OF    DATA   COLLECTED.  7 

Never  give  ncetanilid  or  niiy  like  iireiiarnlion  when  tlieie  is  reason  tliat  some 
(Irns  sbould  be  triven  to  snpport  the  heart  while  this  drn;;  is  acting. 

Give  it  as  a  rule  for  its  sedative  effect  on  the  nervous  system  durins  sthenic 
fevers  rather  than  as  an  antipyretic. 

You  have  not  asked  for  the  above,  but  I  can  not  help  thinkiuR  that  the  war 
made  on  these  drugs  is  carrying  the  matter  to  the  extreme,  and  that  their  dis- 
favor is  due  rather  to  the  excessive  dosage  and  promiscuous  usage  than  to  the 
fact  that  they  are  drugs  not  to  be  used  at  all.  and  in  your  investigation  I  would 
ask  your  earnest  consideration  of  this  aspect  of  the  case. 

To  this  communication  the  Department  of  Agriculture  replied  as 
follows : 

Your  favor  of  June  9  at  hand  and  in  reply  we  desire  to  thank  you  for  the  in- 
formation submitted.  With  regard  to  the  effects  of  ncetanilid  we  would  say  that 
our  views  accord  fully  with  your  own  as  set  forth  in  your  communication,  and 
we  would  be  ]>leased  to  publish  your  letter  in  the  forthcoming  bulletin  of  the 
Department  of  Agriculture  if  it  can  be  used  to  advantage  and  if  you  have  no 
objection.  We  agree  with  you  that  the  barm  done  by  acetanilid  does  not  result 
from  its  proper  use  under  the  direction  of  the  pliysician,  but  is  mainly  the  result 
of  the  i)romiscuous  and  indiscriminate  use  of  the  product  by  the  laity.  The 
(tbject  of  our  investigation  is  not  to  conduct  a  war  against  acetanilid  and  similar 
drugs,  as  you  suggest,  but  rather  to  throw  safeguards  around  the  public  and 
(bus  prevent,  as  far  as  possible,  a  repetition  of  the  many  unfortunate  accidents 
wliicli  are  reported  to  have  resulted  from  the  ill-advised  use  of  these  remedies 
in  the  past. 

Much  has  already  been  accomplished  along  this  line  through  the 
agency  of  the  food  and  drugs  act,  which  requires  that  the  label  of 
medicinal  preparations  shall  contain  information  relative  to  the 
quantity  or  proportion  of  certain  ingredients,  Avhicli  are  entmierated 
in  the  law,  and  their  derivatives  and  preparations.  By  far  the 
greater  number  of  manufacturers  have  shown  a  disposition  to  com- 
pl}'  with  the  law  in  declaring  the  prescribed  drugs,  but  an  investi- 
gation shows  that  many  preparations  containing  these  or  other  dan- 
gerous agents  Ijear  statements  which  transgress  the  section  of  the 
law  on  misbranding.  The  misrepresentation  in  many  instances  takes 
the  form  of  assertions  to  the  effect  that  the  remedy  is  harmless  or 
tliat  it  contains  no  poisonous  or  harmful  ingredients.  Again,  the 
public  is  given  to  understand  in  many  cases  that  the  medicine  can  be 
taken  practically  ad  libitum  until  the  desired  effect  is  obtained. 

Some  of  the  manufacturers  of  acetanilid  preparations,  not  content 
with  claiming  that  their  products  contain  no  poisonous  or  harmful 
ingredients,  go  even  further  and  assert  that  the  medicine,  in  addition 
to  being  an  efficient  remedy,  acts  as  food  or  nourishment  for  the  up- 
building of  some  particular  part  of  the  body;  that  it  is,  in  short,  a 
"  nerve  food  "  or  a  "  brain  food."  With  regard  to  this  use  of  the 
word  "  food  "  the  judgt;  in  the  case  above  referred  to  in  his  charge 
to  the  jury  spoke;  as  follows: 

If  that  word  ["itrain  food"!,  spelled  in  llie  two  differeni  ways  (bat  it  Is 
spelled,  would  fonvey  'o  lli<'  ordinary  citizen   llic  idea   thai    it    was  a   food   for 


8 


ACETANILID,   ANTIPYRIN,   AND   PHENACETIN. 


the  brain  as  contradistinguished  from  the  idea  of  a  food  for  the  whole  body, 
then  it  is — and  I  so  charge  you  in  this  tirst  prayer — misleading,  and  therefore 
a  violation  of  the  law. 

The  information  submitted  in  the  following  pages  with  regard  to 
the  nmnber  of  instances  quoted  in  the  literature  of  the  subject  in 
which  poisoning,  death,  or  habitual  use  has  been  known  to  result 
from  the  administration  of  acetanilid,  antipyrin,  and  acetphenetidin 
is  summarized  in  section  A  of  the  table  following. 

The  information  as  tabulated  in  section  B  was  furnished  by  400 
physicians,  in  reply  to  letters  of  inquiry  issued  by  the  Department. 
Nine  hundred  and  twenty-five  of  these  letters  were  sent  out,  and  400 
replies  were  received.  Granting  that  the  525  physicians  who  did  not 
reply  had  no  cases  to  report,  the  question  may  profitably  be  asked,  if 
925  physicians  have  observed  814  cases  of  poisoning  by  these  drugs, 
28  deaths  which  were  attributed  to  their  use,  and  136  instances  of 
habitual  use,  how  many  such  cases  have  in  all  probability  been  ob- 
served by  the  125,000  physicians  scattered  throughout  the  United 
States?  The  first  summary,  C,  includes  both  the  number  of  cases 
recorded  in  medical  literature  and  those  reported  by  physicians. 

Cases  in  which  deleterious  or  fatal  effects  have  been  produced  by  acetanilid,  antipyrin,  and 

acetphenetidin. 

A.  CASES  RECORDED  IN  MEDICAL  LITERATURE,  1884-1907. 


Substance. 

Poison- 
ing. 

Deaths. 

13 

10 

3 

Habitual 
use. 

Acetanilid 

297 

488 
70 

32 

Antipyrin 

Acetphenetidin 

1 

Total 

855 

26 

33 

B.  DATA  REPORTED  BY  PHYSICIANS. 


Acetan  ilid 

014 
105 
95 

16 
5 

7 

112 

Antipyrin 

7 

Acetphenetidin 

17 

Total 

814 

28 

l;6 

C.  TOTAL  OF  COLLATED  CASES  (A  AND 

B). 

Acetanilid 

911 
.593 
165 

29 
15 
10 

144 

7 
18 

Antipyrin 

Acetphenetidin 

General  total 

1,669 

54 

169 

REPORTS    OF    PHYSICIANS.  9 

REPORTS  OF  PHYSICIANS  WITH  REGARD  TO  PERSONAL  EXPERI- 
ENCE IN  THE  USE  OF  ACETANILID,  ANTIPYRIN,  AND  ACET- 
PHENETIDIN  (PHENACETIN). 

For  the  purpose  of  obtaining  information  with  regard  to  the 
poisonous  eli'ects  of  acetanilid,  antipyrin,  and  phenacetin  from  the 
viewpoint  of  personal  experience  and  observation,  the  following  letter 
of  inquiry  was  addressed  by  the  Department  of  Agriculture  to  medical 
practitioners  in  the  United  States: 

United  States  Department  of  Agriculture, 

Bureau  of  Chemistry, 
Washington,  D.  C,  June  1,  1908. 
Dear  Sir:  We  are  collecting  inforuiatiou  relative  to  the  poisonous  nature  of 
acetanilid,  antipyrin,  and  phenacetin,  and  in  order  to  make  the  data  as  com- 
plete as  possible  I  am  sendinij;  you  a  number  of  questions  and  would  ask  that 
you  supi)ly  the  information  requested  at  your  earliest  convenience.  If  there  is 
not  sutticient  space  allowed  to  give  all  the  data  you  may  possess  it  is  expected 
that  you  will  use  the  blank  pages  of  the  folder,  making  the  statement  as  concise 
as  possible. 

The  information  requested  is  for  the  use  of  the  Department  in  comi)iling  a 
bulletin,  and  general  cretllt  will  be  given  for  all  data  supplied.  An  early  reply 
will  be  much  appreciated. 

Respectfully,  H.  W.  Wiley,  Chief. 

Following  ar*e  the  questions  referred  to  in  this  communication,  tlie 
inquiries  relating  in  each  instance  to  the  three  drugs— acetanilid, 
antipyrin,  and  phenacetin: 

1.  To  what  extent  do  you  use  these  drugs  in  your  ])ractice? 

2.  What  dose  do  you  ordinarily  i)rescribe  for  adultsV 

3.  Do  you  prescribe  them  more  or  less  freipiently  than  formerly?     Why? 

4.  What    is   your   (»i)inion    with    regard   to   the   relative   safety   of   these   three 

drugs V 
f).  Have  you    observed    instances  of   acute  or  chronic   poisoning  or   cyanosis 

caused  by  these  drugs?     How  many  of  each? 
0.  In  what  form  was  the  drug  administered? 
7.  About  what  dates  did  tiie  poisoning  occur? 

5.  Were  the  patients  adults  or  children? 
1>.  For  what  ailment  was  the  drug  taken? 

10.  Was  it  ordered  by  a  physician? 

11.  Was  it  used  internally  or  externally? 

12.  Quantity  taken? 

I.'J.  Give  brief  history  of  cases  observed  by  you,  omitting  details. 

14.  Have  you  ol).served  any  cases  of  habitual  use  of  any  of  these  drugs  or  of  any 

jtrepiirations  containing  them? 
I.'J.  In  what  form  was  the  drug  taken? 

16.  Were  there  any  ill  effects?     (Jive?  brief  description. 

17.  Were  there  any  protracted  ill  efl'e<"ts? 

18.  Give  a  brief  clinical  liistory  of  each  case. 

This  lettci'  of  inquiry  was  sent  (o  physicians  (Inoughoiil  the  Fuitcd 
►States,  (he  oljject  bcurig  to  secure  inroiinalion  which  woiihl  represent 


10 


ACETANILID,    ANTIPYRIN,   AND   PHENACETIN. 


as  closely  as  possible  the  conditions  existing  among  the  people  at 
large,  so  far  as  the  harmful  effects  of  acetanilid,  antipyrin,  and 
phenacetin  are  concerned.  Much  information  relative  to  poisoning 
by  these  drugs  could  have  been  obtained  from  the  records  of  hospitals, 
particularly  those  located  in  the  larger  cities,  but  it  was  thought  that 
information  from  this  source  would  not  be  of  a  strictly  representative 
character.  The  conditions  aifecting  hospital  patients  differ  from 
those  surrounding  patients  in  private  homes,  and  this  difference  is 
particularly  marked  in  the  case  of  the  drugs  under  consideration. 
For  this  reason  it  was  deemed  advisable  to  secure  the  desired  informa- 
tion from  physicians  at  large  rather  than  from  hospital  records. 

Four  hundred  replies  were  received  to  the  925  letters  sent  out,  and 
the  information  submitted  is  set  forth  in  the  following  pages. 

Question  1. — To  what  Extent  do  you  Use  these  Drugs   (Acetanilid,  Anti- 
pyrin, Phenacetin)  in  your  Practice? 


Extent  of  use. 


Frequently 

Moderately 

Oceasionaily 

Rarely 

Only  in  pertussis . 

Externally 

Never  


Total  number  of  observers 


Number  of  replies. 


Acetanilid.  Antipyrin.   Phenacetin, 


90 
30 
62 
100 


6 
112 


9 
11 
61 
99 
14 

8 
208 


109 
38 
73 


94 
400 


From  this  it  would  appear  that  acetanilid  is  used  frequently  or 
moderately  by  120,  or  30  per  cent,  of  the  physicians;  antipyrin  by 
only  20,  or  5  per  cent;  and  phenacetin  by  147,  or  36.7  per  cent.  On 
the  other  hand,  112,  or  28  per  cent,  of  the  physicians  state  that  they 
do  not  use  acetanilid  at  all ;  and  100,  or  25  per  cent,  use  it  but  rarely ; 
208,  or  52  per  cent,  never  use  antipyrin,  and  90,  or  25  per  cent,  use 
it  but  rarely ;  94,  or  23.5  per  cent,  of  observers  never  use  phenacetin ; 
and  8G,  or'  21.5  per  cent,  employ  it  but  rarely. 

Thus,  of  the  three  drugs  phenacetin  appears  to  be  most  used  by 
physicians,  with  acetanilid  second,  while  antipyrin  is  apparently  used 
to  a  much  less  extent  than  either  of  the  others,  only  5  per  cent  of  the 
physicians  stating  that  they  employ  it  frequently  or  moderately.  The 
reason  for  the  more  extensive  use  of  phenacetin  is  undoubtedly  to  be 
found  in  the  fact  that  it  is  generally  regarded  as  being  the  least  harm- 
ful of  these  agents.  This  was  indicated  particularly  in  the  answers 
to  question  No.  4. 


EEPORTS    OF    PHYSICIANS.  11 

Question  2. — What  Dose  do  you  Ordinarily  Prescribe  for  Adults? 


Acetanilid. 

Antipyrin. 

Phenacetin. 

Dose. 

Number 

of  ob- 

.servers. 

Dose. 

Number 
of  ob- 
servers. 

Dose. 

Number 
of  ob- 
servers. 

Grains. 
0.5 

1 
2 
1 
1 
2 
7 
2 
1 

25 

15 
9 

19 
1 

18 
9 

32 
3 
2 

39 
2 
1 
9 
6 
1 
1 

38 
3 
6 

12 
1 
1 
2 
1 
1 

Grains. 
0.5to2.5 

1 
1 
2 
1 
1 
1 
2 
3 
5 
4 
3 

15 
1 
1 
1 
1 
1 
1 

25 
8 

26 
5 
5 
8 
2 
1 

ir, 
1 

2 
2 
1 

1 
1 

1 

Grains. 
0  5  to  6 

1 

0.5  to  1 

1 

1 

1 

0.5  to  10 

1  to2 

1  to  2 

1 

I 

1  to  10 

1  to  2  5. . 

] 

1  to  2 

1.5 

1  to  6 

•> 

1  to  3 

2 

1.5  to  2.5 

■I 

1  to  5 

2  to  3 

2 

10 

l.f) 

2  to  4 

2  to  3 

13 

2  to  5 

2  to  4 

2  to  3 

2.5 

3...   . 

2  to  6 

:il 

2  to  4  . 

2  to  6 

2  to  7  5 

1 

2  to  5 

3  to  5 

1 

2  to  7. 5 

3  to  10 

2  to  10  . 

1 

2.5 

3  to  15 

2  to  20 

1 

2  5  to  3 

3.5 

4 

2  5 

]('> 

3 

2  5  to  7  5 

1 

3to3.5 

4  to  5 

3 

4 

3  to  4 

4  to  6 

27 

3  to  5 

5 

3  to  6 

2 

3to  6 

5  to  7.5 

3  to  8 

3 

3  to  7.5 

5  to  10  . . 

3  to  15 

1 

3.5 

5  to  15 

4 

3 

4 

7.5 

4  to  5 

2 

4  to  8 

4 

4t<^)12 

S 

5 

S7 

5 

8  to  10  . . 

5  to  6 ... 

6  to  7  5 

1 

10 

14 

5  to  8 

10  to  12  5 

5  to  S  .     . 

2 

5  to  10  ... 

10  to  15  . 

6tol0 

5  to  15 

G 

7  to  8 

35 

fi  tolO 

10  to  20 

12  to  15  . 

3 

7 

2 

7  5 

12  5 

1 

7.5  to  10. 

15 

7  to  10 

2 

10 

Up  to  20 

7.5 

1 

s 

2 

8  to  10  

1 

10 

10  to  12 

7 
1 

10  to  20 

2 

SUMMARY. 


.NiiiiilMT  statinp  dose .. 
.Number  wbo  <lid  not.. 
.Number     who     u.«ed 

druK 

-Number  who  did  not.. 


271 
14 


288 
112 


Numlter  statintr  dose . 
Number  who  (lid  not. 
Numl)er    wlio    used 

druff 

Number  wlio  did  not. 


150 

42 


192 
208 


Number  slatiiifr  do.so . 
Number  who  (lid  not. 
Numl)er    wlio     ii.sed 

dniR- 

Number  who  did  not. 


297 
9 


30r> 
94 


From  this  it  would  appear  that  out  of  274  observers  who  stated 
that  they  use  aeetauilid  IT,  or  0.2  j)er  cent,  empk)y  less  than  2  f^rains 
as  a  mininiiiin  dose  for  adults;  113,  or  41.2  per  cent,  employ  2.5 
j^ains  or  less  as  a  minimum  dose;  and  155,  or  5(5.5  per  cent,  employ 
from  3  to  5  grains  as  a  minimum  dose.  Two  hundred  and  forty,  or 
a  little  over  87.5  per  cent,  never  exceed  a  dose  of  5  grains,  and  34, 
or  not  quite  12.5  per  cent,  employ  doses  exceeding  5  grains. 

With   regard  to  antipyrin   only  23,  or  15.3  per  cent  of  the   150 

.l>s("rvers  who  stated  that  they  use  this  di-ug,  exceed  a  dose  of  10 

grains,  while  00,  or  44  per  cent,  never  exceed  a  dose  of  5  grains; 


12  ACETANILID,   ANTIPYEIN,   AND   PHENACETIN. 

and  109,  or  72.6  per  cent,  employ  5  grains  or  less  as  a  minimum 
dose. 

Out  of  297  observers  using  phenacetin  10,  or  3.3  per  cent,  employ 
less  than  2  grains  as  a  minimum  dose;  90,  or  30.3  per  cent,  employ 
2.5  grains  or  less  as  a  minimum  dose;  188,  or  63.3  per  cent,  employ 
from  3  to  5  grains  as  a  minimum  dose ;  89,  or  29.9  per  cent,  use  doses 
exceeding  5  grains;  while  208,  or  70  per  cent,  never  exceed  a  dose  of 
5  grains. 

From  this  it  seems  reasonable  to  conclude  that  the  doses  of  these 
remedies  which  are  prescribed  to-day  are  much  smaller  than  those 
which  were  formerly  employed.  The  report  of  the  therapeutic 
committee  of  the  British  Medical  Association  with  regard  to  the  ill 
effects  of  acetanilid,  antipyrin,  and  phenacetin,  published  in  1891, 
a  summarj^  of  which  appears  on  page  20,  made  a  deep  impression 
on  the  medical  mind,  and  undoubtedly  did  much  to  bring  about  a 
more  conservative  use  of  these  drugs,  particularly  so  far  as  dosage 
is  concerned.  The  committee  concluded  from  its  investigation  that 
the  ill  effects  which  had  been  ascribed  to  these  remedies  were  very 
largely  the  direct  result  of  injudicious  and  excessive  dosage,  and  in 
harmony  with  this  conclusion  they  suggested  that  they  should  be 
used  with  greater  caution  in  the  future.  Since  that  time  the  doses 
employed  have  been  smaller  than  before,  and  it  has  been  noted  that 
coincidentally  with  this  change  the  number  of  accidents  resulting 
from  the  ingestion  of  these  remedies  has  fallen  off  to  a  remarkable 
extent.  A  point  of  interest  in  connection  with  the  subject  of  dosage 
and  frequency  of  administration  was  brought  out  in  a  recent  trial, 
wliich  involved  the  misbranding  of  a  certain  headache  remedy  con- 
taining among  other  ingredients  acetanilid  and  antipyrin.  The  evi- 
dence presented  showed  that  the  directions  for  use  accompanying 
many  of  these  acetanilid  preparations  are  not  sufficiently  definite  to 
safeguard  the  consumer  against  a  too  frequent  repetition  of  the  dose, 
and,  in  fact,  that  manj^  of  them  advised  a  rejDetition  of  the  dose  until 
the  desired  result  should  be  obtained.  An  examination  of  a  number 
of  prescriptions  for  adults  on  file  in  various  pharmacies  in  Wash- 
ington, D.  C,  brought  into  court  as  evidence,  supplied  the  following- 
information  on  these  points:  (1)  The  average  dose  of  acetanilid  pre- 
scribed was  2.43  gTains,  and  of  phenacetin  1.92  grains;  (2)  the 
average  interval  between  doses  was,  in  case  of  the  two  remedies, 
3.03  hours. 


REPORTS    OF    PHYSICIANS. 


13 


Question  3. — Do  you  ruKscKiiiE  Thkm   moke  ou  j.kss  FKiXiUKNTLV  than  Fok- 

merlyV     WhyV 


Less  frequently 

More  frecuR'iitly 

To  sjime  i-xtent 

Totiil  iitimber  answering  this  tiiicstioii 

Total  number  not  answering  this  (jiiestion 


Number  of  observers  for — 


Acetanilid. 


179 
13 
79 


271 
129 


Antipyrin. 


135 
265 


Phenace- 
tin. 


143 

4(i 
90 


279 
121 


From  these  fi<2:iu-es  it  -woiikl  app-^^ar  that  acetanilid  is  used  less 
frequently  than  formerly  by  OG  per  cent  of  the  observers,  antipyrin 
by  G5.9  per  cent,  and  phenacetin  by  51.2  per  cent.  Acetanilid  is 
emj^loyed  to  about  the  same  extent  as  formerly  by  21). 1  per  cent, 
antipyrin  by  31.1  per  cent,  and  phenacetin  by  32.2  per  cent  of  ob- 
servers. Only  4.7  per  cent  use  acetanilid  and  1(').4  per  cent  use 
phenacetin  more  frecpiently  than  formerly.  The  reasons  given  for 
the  less  frequent  use  of  these  drugs  are  in  most  instances  their  toxicity 
and  particularly  their  depressing  effects. 

(H'KSTioN  4. — What  i.s  Your  Otinion  with  Rkgakd  to  thk  Kklative  Safety  of 

THESE    DUUGSV 

P'ifty-eight  observers  replied  that  acetanilid  was  the  least  danger- 
ous, 18  named  antipyrin,  and  231  named  phenacetin.  Thirty-seven,  or 
over  10  per  cent,  stated  that  in  their  opinion  there  is  but  little  differ- 
ence between  the  tliree  as  far  as  toxicity  is  concerned,  one  being  about 
as  powerful  a  depressant  as  the  others.  P"ifty-six  did  not  reply  to  this 
(jiiestion.  The  figures  indicate  that  phenacetin  is  regarded  as  the  least 
dangerous  of  these  three  agents  l)y  231  out  of  344  observers,  or  G7.4 
per  cent;  acetanilid  by  58  observers,  or  1G.8  per  cent;  and  antipyrin 
l)y  18,  or  5.2  per  cent. 

Question  5. — Have  you  Observed  Instances  of  Acute  or  Chronic  I'oisonin*; 
OK  Cyanosis  Caused  by  these  Drugs?    How  Many  of  EachV 


EflectH  profliiccd. 


ADULTS. 

A<-Mt<!  jxiinoiiiii),' 

ChroiiKr  |>oi>onin)f 

(■yaniwis 

Acute,  fatal 

Total  number  of  cwwn  reported 

r  IIII.DKKS. 

Acute  |>oi.>4onin(; 

( 'yHiioHix 

Acute,  fatal 

Total  number  of  caMcw  reported 

Total  number  of  cattes,  udultji  und  cliildren 

7 


Number  of  cases. 

Aeetjinilid. 

2«4 
12 

213 
10 

Antipyrin. 

I'henaer 

•tin. 

69 

4H 
2 

14 
4 

•    28 

.519 

H7 

H 

54 
4 
7 

17 

10 

1 

1 

Ofi 

IH 

11 

fil4 

lO,') 

n 

14  ACETANILID,    ANTIPYRIN,   AND    PHENACETIN. 

Out  of  288  i:)ractitioners  who  submitted  an  answer  to  this  question 
in  regard  to  acetanilid,  219,  or  76  per  cent,  stated  that  they  had  ob- 
served instances  of  poisoning  following  the  use  of  this  drug.  These 
219  observers  report  614  cases  of  poisoning,  including  17  deaths. 
Eighty-nine,  or  46.3  per  cent,  of  the  192  physicians  who  submitted 
similar  information  with  regard  to  antipyrin  stated  that  they  had 
observed  toxic  effects  and  reported  105  cases,  including  5  deaths.  Of 
306  physicians  who  submitted  data  on  phenacetin,  66,  or  21.5  per  cent, 
reported  95  cases  of  poisoning,  including  7  deaths. 

Of  the  614  cases  of  poisoning  which  are  said  to  have  resulted  from 
the  ingestion  of  acetanilid,  17,  or  2.7  per  cent,  terminated  fatally;  of 
the  105  cases  of  antipyrin  poisoning,  5,  or  4.7  per  cent,  resulted  fa- 
tally; and  of  the  95  cases  of  poisoning  by  phenacetin,  7,  or  7.3  per 
cent,  terminated  fatally.  Additional  information  with  regard  to  the 
fatal  cases  follows : 

ACETANILID. 

Pueumonia  (child) One-lialf  grain   every  two  lionrs  until  2  grains 

were  taken. 
Capillary broncliitis  (child)--  Small  doses  frequently  repeated. 

Capillary  bronchitis  (child) Small  doses  frequently  repeated. 

Typhoid Five  grains  every  four  hours. 

Headache About  20  grains. 

Headache Thirty  grains  (?) 

Headache "Orangeine"  taken  freely. 

Headache Thirteen    or    fourteen    5-grain    doses    in    twelve 

hours. 

Headache Bromo-seltzer. 

Neuralgia Dose  not  given. 

Neuralgia  of  heart Five  5-grain  doses  in  five  hours. 

Burn Boroacetanilid  applied  freely. 

Burn  (infant) Acetanilid  applied  freely  to  umbilical  cord. 

Headache Excessive  dose  of  "  bromo-seltzer." 

Typhoid  (child) Five  grains. 

Typhoid  (child) Doseuot  given. 

Malaria  (child) One  and  one-half  grains. 

ANTIPYRIN. 

Pneumonia Ten  grains  every  two  to  three  hours.     Death  on 

third  day. 

Fever   (child) Twenty  grains.     Death  in  two  hours. 

Acute  rheumatism Antipyrin  dispensed  instead  of  "Aspirin."  Quan- 
tity not  stated.    Patient  died  suddenly. 

Headache- Ten  grains,  followed  by  15  grains  in  an  hour. 

Neuralgia Five    grains    every    three    to    four    hours.      One 

drachm  taken  in  two  days. 


REPORTS    OF    PHYSICIANS. 


15 


PHENACETIN. 

I'ueniuouia Seventy  grains  daily  for  two  days;  died  suddenly. 

Influenza Five  grains  every  three  liours;  not  over  G  doses. 

Broucliitis  (1  year) Two  grains  every  three  hours;  five  doses;  died 

twelve  hours  after  last  dose. 
Typhoid Two  and  one-half  grains  every  two  hours  until 

1  scruple  was  taken. 

Headache. Ten  grains. 

Headache  (cerebral  tumor) Fifteen  grains  in  twelve  liours. 

Woman,  aged  TO Two  3-grain  doses  two  hours  apart. 


Question  G. — In  What  Form  was  the  Drug  Administered? 
[In  cases  of  poisoniug.] 


Form. 


Powder 

Tablets 

EiJls 

In  solution 

Form  not  stated 


Number  of  cases. 


Acetanilid. 


425 

1(;3 

6 

4 

ii; 


Antipyrin. 


I'henace- 
tiu. 


The  form  in  which  the  drug  was  administered  in  the  cases  of  i)ois- 
oning  above  mentioned  is  set  forth  in  the  accompanying  table.  Pro- 
prietary preparations  containing  acetanilid  were  reported  to  have 
been  used  in  77  or  12.5  per  cent  of  the  cases. 

Question  7.-^xVbout  What  Dates  did  the  I'oisonino  Occur? 


Number  of  cases. 

Year. 

Number  of  cases. 

Year. 

Acet<viii- 
lid. 

Antipyrin. 

Phenace- 
tin. 

Acetani- 
lid. 

.'Vntipyrin. 

Plienace- 
tin. 

IS!^ 

G 
1 
6 

•2 
7 
1 

N 

7 
13 
•J8 
10 
27 

5 
1 
3 
4 
I 

1901 

IG 
10 
:;() 
17 
:t2 
i'i 

IH 
18 

32.5 

]ss9 

IIKVJ 

2 

3 

1M90 

]'.103 

]'.)04 

3 

18'JI .     . 

1 

5 

18i>2 

2 
2 

1905 

5 

IS93 

1906 

1 
3 

1 

1S94 

3 
7 
3 
f) 
3 
2 

1907 

7 

1S93 



2 

1 

1908 

3 

1896 

No       dalt! 
fe'iveii 

Total... 

55 

1897 

52 

1X98 

5 

Gil 

105 

lM'.t9 

95 

1900 

1 

Question  8. 

— WEKE  the   I'AliKNTS   ADI'I. 

IS  ou  (  'lIll.ltltKN? 

Af,"- 

if  |pali<-iil. 

Number  of  cfwes. 

A<eUnilid. 

549 
05 

Anlipyriti. 

I'llrlm.'- 
cliii. 

87 
18 

84 

11 

Tota  1 

G14 

106 

96 

16  ACBTANILID,    ANTIPYRIN,   AND    PHENACETIN. 

Question  9. — For  What  Ailment  was  the  Deug  Taken? 


Number  of  cases. 

Ailment. 

Number  of  cases. 

Ailment. 

Acetani- 
lid. 

Anti- 
pyrin. 

Phenac- 
etin. 

Acetani- 
lid. 

Anti- 
pyrin. 

Phenac- 
etin. 

ADULTS. 

380 
46 

83 

25 
15 
43 

41 

4 

34 

1 

CHILDREN. 

3 

44 

Fever 

5 
10 

11 

Pertussis 

Colic 

1 

i 

Convulsions 

1 

Accidentally 

Suicidal  intent 

Externally    to 
wounds  ..y 

1 

1 

9 
29 

Externally    to 

5 
12 

Not  stated 

2 

Total 

3 

4 

65 

18 

11 

1 
i 

Total 

549 

87 

84 

Question  10. — Was  it  Ordered  by  a  Physician? 


Number  of  cases. 

Administration. 

Acetanilid. 

Antipyrin. 

Phenac- 

etin. 

289 
325 

79 
26 

69 

26 

Total 

614 

105 

95 

These  figures  show  that  in  more  than  one-half  of  the  cases  of  poi- 
soning the  drugs  were  taken  by  direction  of  a  physician.  This  fact  is 
especially  significant  in  connection  with  the  ever-increasing  sale  of 
these  agents,  and  preparations  containing  them,  directly  to  the  public. 
In  such  cases  the  remedy  is  taken  by  the  patient  without  proper  med- 
ical advice  and  supervision,  and  its  administration  is  not  surrounded 
by  the  safeguards  which  ordinarily  attend  the  ingestion  of  medicine 
which  has  been  prescribed  by  a  physician.  Under  these  circumstances 
it  is  not  strange  that  ill  effects  are  observed  with  comparative  fre- 
quency. If,  moreover,  poisoning  occasionally  results  from  the  use 
of  these  remedies  even  as  prescribed  by  the  physician,  should  not  the 
greatest  caution  be  observed  by  the  laity  in  taking  them  without 
the  safeguard  of  medical  advice  ?  The  first  and  most  important  step 
in  the  prevention  of  these  accidents  appears  to  be  to  impress  on  the 
members  of  the  community  the  fact  that  these  drugs  are  by  no  means 
harmless,  but,  on  the  contrary,  are  capable  of  producing  serious  ill 
eifects  when  used  injudiciously. 

Question  11. — Was  It  Used  Internally  or  Externally? 


How  used. 

Number  of  cases. 

Acetanilid. 

Antipyrin. 

Phenacetin. 

Internally 

600 
14 

105 

95 

Externally 

Total 

614 

105 

95 

REPORTS    OF    PHYSICIANS. 


17 


Poisoninc:  resulted  from  the  external  application  of  acetanilid  in 
Irt,  or  nearly  2.3  per  cent,  of  the  cases.  This  is  interesting  as  it  illus- 
trates the  toxic  power  of  the  drug.  Xo  poisonous  effects  are  reported 
to  have  been  observed  from  the  local  application  of  either  antipyrin 
or  phenacetin. 

Question  12. — Quantity  Taken  in  Cases  of  Poisoning. 

ADII.TS. 


Acetanilid. 


Dose  (grains). 


0.5 

1 

2'to^'.'.'.'.'.'.'.'.'..'. 

2tol0 

2.5 

3to3.5 

3tolO 

4 

5 

5to6 

5to8 

otOlO 

5tol5 

7 

10 

10  to  15 

10  to  20 

10to60 

12 

15 

15to20 

15  to  25 

15to30 

20 

25 

30 

40 

60  

90 

120 

200 

Teaspoonf  ul . . . 
External  cases 
Fatal  cases". . . 
Dose  not  stated 

Total.... 


Number 
of  cases. 


Antipyrin. 


Dose  (grains). 


Number 

of  cases. 


2to5 

5 

5tol0 

8 

10 

10  to  15 

10  to  20 

10  to  30 

15 

Less  than  20  . . . 

20 

30 

40 

45 

60 

Fatal  cases  a... 
Dose  not  stated 


ri4'j 


Total 


Phenacetin. 


Dose  (grains). 


Number 
of  cases. 


2to5 

3 

3  to  5 

6 

5  to  10 

6tol5 

10 

10  to  12 

10  to  20 

12 

15 

20 

30 

70 

yu 

100 

Fatal  caseso 

Dose  not  stated. 


Total 


("IIIMIKKN. 


0.06 

1 

2 

2U)S 

8 

5 

6to6 

I>e«s  than  10  . . . 
Kxt«Tnal  ca>es 
Fatal  cases".. . 
DoM:  not  stated 

Total  . . . . 


0  5 

1 

3to6        

1 

5     

1 

8  to  10       

3 

10 

1 

1 

Dose  not  stated 

10 

Total 

18 

'  See  pnge  14. 


82.'il0— P.iill.  120— (»;» 


18  ACETANILID,    ANTIPYRIN,    AND    PHENACETIN. 

Out  of  the  368  cases  in  which  the  dose  of  acetanilid  administered 
to  adults  was  stated,  the  poisoning  was  caused  by  doses  of  5  grains  or 
more  in  331,  or  89.9  per  cent;  with  antipyrin  the  ill  effects  were 
caused  by  doses  of  10  grains  or  more  in  89.T  per  cent  of  the  cases. 
while  with  phenacetin  the  toxic  effects  were  caused  by  doses  of  10 
grains  or  more  in  G7.8  per  cent  of  the  cases,  and  by  doses  of  5  grains 
or  more  in  93.2  per  cent  of  the  cases. 

In  85.7  per  cent  of  the  cases  the  poisonous  effects  of  acetanilid  ad- 
ministered to  children  were  caused  by  doses  of  2  grains  or  more ;  with 
antipyrin  the  ill  effects  were  due  to  doses  of  3  grains  or  more  in  85.7 
per  cent  of  the  cases,  while  with  phenacetin  no  ill  effects  were  re- 
ported to  have  resulted  from  doses  under  2  grains. 

Question    13. — Give    Brief    History    of    Cases    Observed    by    You,    Omitting 

Details. 

The  information  submitted  in  answer  to  this  inquiry  is  given  in 
connection  with  the  replies  to  the  remaining  questions. 

Question  14. — Have  You  Observed  Any  Cases  of  Habitual  Use  of  Any  of 
These  Drugs  or  of  Any  Preparation  Containing  Them? 

An  endeavor  was  made  to  obtain  information  with  regard  to  the 
extent  to  which  these  drugs  are  used  habitually,  as  it  has  long  been 
known  that  acetanilid,  antipyrin,  and  phenacetin  are  habit-forming 
drugs,  particularly  acetanilid.  The  habit  is  acquired  in  most  in- 
stances through  the  use  of  the  remedy  without  the  supervision  of  the 
physician  for  the  relief  of  minor  aches  and  pains,  especially  headache. 
These  affections  are  usually  of  a  recurrent  character  and,  the  remedy 
exerting  but  a  palliative  effect,  the  dose  after  a  time  must  be  repeated 
and  in  time  the  patient  may  become  dependent  on  the  drug.  Further- 
more, the  prolonged  or  habitual  use  of  these  agents  tends  to  produce 
an  impaired  condition  of  the  general  health  w^hich,  as  in  all  such 
cases,  is  accompanied  by  a  lessened  resistance  on  the  part  of  the 
body  to  disease.  Under  these  circumstances  the  affection  for  which 
the  remedy  was  originally  taken  assumes  greater  proportions  than 
ever,  and  as  a  result  there  is  additional  call  for  the  drug.  Thus  a 
vicious  circle  is  established — more  drug,  imj^aired  bodily  health, 
lessened  resistance,  more  pain,  more  drug. 

It  has  been  said  that  in  its  baneful  effects  on  the  system  and  in 
the  difficulty  which  is  experienced  in  giving  up  the  use  of  these 
drugs  in  many  instances,  the  habit  ranks  as  an  evil  with  the  opium 
habit.  Whether  this  is  true  or  not,  there  can  be  no  reasonable  doubt 
that  their  prolonged  or  habitual  use  is  decidedly  harmful  to  the  sys- 
tem. In  spite  of  this  fact,  the  habitual  use  of  these  agents  is  spread- 
ing among  the  people  and  it  is  becoming  more  and  more  apparent 


EEPORTS    OF    PHYSICIANS. 


19 


that  an  eH'ort  should  be  made  to  acquaint  the  general  public  with 
the  ill  effects  which  may  reasonably  be  expected  to  follow  such  use. 

In  rei)ly  to  the  inquiry  by  the  Department,  112  instances  of  the 
acetanilid  habit  were  reported,  7  of  the  antipyrin  habit,  and  17  of 
the  phenacetin  habit.  It  should  be  remembered,  however,  that  neither 
these  cases  nor  those  which  are  recorded  in  medical  literature  give 
an  adecpiate  indication  of  the  extent  to  which  these  drugs  are  used 
habitually,  inasmuch  as  onl}'  those  cases  have  been  reported  in  which 
the  ill  effects  were  so  marked  as  to  call  for  the  services  of  a  ph^'sician. 
Interesting  information  with  regard  to  the  habitual  use  of  these  drugs 
can  be  obtained,  by  consulting  the  original  reports  of  the  cases  re- 
corded in  medical  literature. 

Question  15. — In  what  Form  was  thic  Drug  Taken"? 

llu  tilt'  case  of  habitual  users.] 


« 

Number  of  cases. 

Form— 

Acetani- 
lid. 

Anti- 
pyrin. 

I'heiiac- 
etin. 

I'owdcrs .        

29 

25 

7 

12 

Tablets 

4 

In  solution 

1 

50 

8 

Fonn  not  stated 

Total 

112  1                    7 

17 

From  this  it  appears  that  proprietary  preparations  were  used  in  at 
least  50,  or  14.G  per  cent,  of  the  112  instances  of  the  habitual  use  of 
acetanilid. 


Question  l(i. — Were  Thp:re  Any  III  Effects V     (Jive  Description. 

The  number  of  cases  in  which  ill  effects  were  observed  from  the 
use  of  acetanilid  was  8'),  from  antij)vrin  2,  and  from  ])heiiacetin  7. 
The  chief  symptoms  observed  from  the  habitual  use  of  these  drugs 
may  be  briefly  classified  as  follows:  Nervous  depression,  44  cases; 
cyanosis,  27  cases;  anemia,  15  cases;  cardiac  depression,  18  cases; 
dyspnea  on  exertion,  8  cases;  insouinia,  4  cases;  constipation,  3  cases; 
loss  of  memory,  3  cases;  icterus,  1  case;  muscular  twitchings,  1  case; 
loss  of  sexual  power,  1  case;  edema,  2  cases,  and  increased  headache, 
2  ca.ses. 

Question  17. — Were  There  Any  I'rotracted  Ile  EfkecisV 

The  replies  submitted  in  answer  to  tliis  question  show  (hat  ]iro- 
tracted  ill  effects  were  ob.served  in  the  case  of  acetanilid  in  38  in- 
stances, with  antipyrin  in  2  instances,  and  with  |)henacetin  in  5  in- 
.stances.  The  (rhroni(;  symptoms  most  often  nolecl  were  anemia,  gen- 
eral debility,  nervousness,  and  weak  and  irregular  heart  action. 


20  ACETANILID,   ANTIPYKIN,   AND   PHENACETIN. 

Question  IS. — Give  a  Bkief  Clinical  History  of  Each  Case. 

The  information  submitted  in  answer  to  this  question  is  embodied 
in  the  data  presented  in  tlie  preceding  pages. 


AN  INQUIRY  REGARDING  THE  IMPORTANCE  OF  ILL  EFFECTS  OF 
THESE  AGENTS,  CONDUCTED  BY  THE  BRITISH  MEDICAL  ASSO- 
CIATION. 

In  1894  a  committee  of  the  British  Medical  Association  known  as 
the  "  therapeutic  committee,"  of  which  Dr.  D.  J.  Leech  was  chair- 
man and  Dr.  William  Hunter  honorary  secretary,  conducted  an  in- 
quiry with  regard  to  "  The  importance  of  the  ill  effects  which  occa- 
sionally attend  the  use  of  the  three  chief  antipyretic  and  analgesic 
agents,  phenazone  (antipyrine),  acetanilide  (antifebrin)  and  phen- 
acetin."  For  the  purpose  of  this  investigation  a  letter  of  inquiry 
was  sent  to  medical  practitioners  in  Great  Britain  requesting  infor- 
mation based  on  j^ersonal  experience  with  these  drugs.  The  replies 
received  in  answer  to  this  letter  furnished  much  valuable  information 
and  the  report  of  the  committee  *  contained  descriptions  of  a  number 
of  cases  of  poisoning.  The  following  summaries  are  taken  from  the 
report  of  the  committee,  and  contain  information  with  regard  to  the 
principal  effects  noted  by  the  different  observers. 

Ill  effects  from  the  administration  of  acetanilid,  antipyrin,  and  phenacetin,  as 
observed  in  Great  Britain. 


[When   the   actual    dose   which    occasioned   the    ill    effect    is    not    stated, 
employed  by  the  observer  is  given  within  parentheses.] 


the    usual    dose 


Nature  of  ill  effects. 


Grains  administered. 


ACETANILID. 


Alarming  collapse  more  than  once 

Excessive  sweating,  cyanosis,  feebleness  of  pulse,  and  partial  collapse, 

comparatively  frequent 

Cyanosis  after  repeated  doses 

Cyanosis  on  two  occasions 

Cyanosis  and  collapse,  once  after  a  double  dose 

Collapse  in  two  children 

Cyanosis  and  collapse  In  one  or  two  cases 

Cyanosis  and  depression 

Do 


Cyanosis 

Collapse  and  death 

Collapse  after  continuous  doses  of  7^  grains 

Collapse  after  10  grains ^ 

Undue  perspiration  and  depression 

Do 

Collapse 

Depression 

Palpitation  and  collapse 

Severe  cyanosis  after  2  doses  of  10  grains  each 

Cyanosis  once 

Cyanosis,  profuse  perspiration,  and  partial  collapse. 
Cyanosis  and  collapse 

Do 

Do ; 

Do 

Collapse  in  phthisis  even  after  2  grains 

Alarming  collapse  in  a  child  by  a  second  dose 


(4). 

(2  to  5). 

(5  to  10). 

7  every  4  hours. 

(10). 

(6  to  10). 

Not  stated. 

{^). 

(10). 

7i. 

Not  stated. 

(5  to  10). 

(2  to  3). 

(5). 

(8). 

(8  to  10). 

(6  to  8). 

(2  to  20). 

(5  to  8). 

(4  to  8). 

(10). 

(8  to  10). 

(3  to  10). 

(5  to  10). 

(8  to  10). 

2. 

3. 


"Brit.  Med.  J.,  London,  1894,  1:  85. 


LITERATURE   ON   ACETANILID   POISONING.  21 

III  effects  from  the  administration  of  acetanilid,  etc. — Continued. 


Nature  of  ill  effects. 


Grains  administered. 


ANTIFVRIN. 

Weakness  and  shakiness 

Serious  collapse  in  a  case  of  typhoid  fever 

Syncopal  attack  on  one  occasion 

Symptoms  of  collapse 

Enfeebling  in  its  action 

Depres.san  t 

Do 

Cardiac  weakness  and  Irregularity 

Great  dejjression 

Great  depression  and  exhaustion 

Alarming  depression 

Cyanosis  and  dangerous  cardiac  depres-sion 

Do 

Depressant  on  heart 

E.xcessive  sweating,  cyanosis,  and  partial  collapse 

Vasomotor  pains,  lividity.  jirofnse  perspiration,  tendency  to  collapse 

and  to  pnenmiinic  congestion 

Cdllnpse  and  death  in  a  case  of  rheumatic  fever 

Ahirmiiig  faintiiess  in  anemic  individuals 

Languor  and  depression 

Weakening  effect  in  10  fier  cent  of  ca.ses 

Serious  cdllapse  in  a  case  of  typhoid 

Los-sof  speech,  lasting  24  hours,  in  a  case  of  commencing  meningitis 

which  subsenuently  proved  fatal 

.\.  condition  of  mania  from  long-continued  use  of  the  drug,  recovered 

from  when  drug  was  withheld 

Dyspnea  and  much  nervous  excitement  once  out  of  many  hundreds  of 

<-ases 

Salivation  with  urticarial  rash  twice  in  same  patient 

Dizziness  and  loss  of  power  in  legs 

PHENACETIN. 

Collapse  on  one  occa.«ion 

Extreme  weakness,  cyano.sis,  and  feebleness  of  pulse 

Cyanosis  once 

Slight  giddiness  once 

Depression,  although  not  often 

Lividity  and  diaphoresis 

Subnormal  temperature,  coldness,  shivering 


(20  to  40). 

30  twice. 

1.5. 

'20. 

(.5  to  20). 

(12  to  20). 

(20). 

1^  every  4  hours. 

30  at  hourly  intervals. 

1.5  every  4  hours. 

4.5  in  8  hours. 

20. 

20. 

(15  to  20). 

(20). 

(30). 

KO  in  5  hours. 

(15  to  20). 

(15). 

20.  repeated  in  an  hour. 

2  (loses  of  30. 

7. 5,  repeated  in  an  hour. 


5  every  3  hours  for  3  days. 

(10  to  15  every  4  hours.) 

7  every  4  hours  for  3  days. 

(5  to  10). 

(5  to  10). 

(10  to  20). 

(5  every  4  hours). 


LITERATURE   ON   POISONING   BY   ACETANILID,    ANTIPYRIN,    AND 
ACETPHENETIDIN     (PHENACETIN). 

ACETANILID. 


I NTRODITC'TOR V    R KSIT M  E, 


The'  followinfj  l>il)liograpliy  contains  references  to  the  rocorderl 
cases  of  poisoning  by  acetanilid  and  preparations  containing  it,  from 
the  date  of  its  introthiction  as  a  medicine  in  1880  to  the  end  of  the 
year  1007,  together  with  a  brief  abstract  of  each  case.  It  was  found 
(o  be  diflicult  in  some  cases  to  draw  the  line  between  cases  of  actual 
j)oisoning  and  cases  in  which  the  symptoms  were  hardly  severe 
enough  to  justify  the  use  of  the  word  "toxic"  in  describing  them. 
The  word  "  poisoning"  as  used  in  the  subsequent  pages  is  inleiuled  to 
include  all  cases  in  which  unexpected,  undesired,  and  deleterious  ef- 
fects resulted  from  the  ingestion  of  acetanilid.  Thus  (he  recorded 
eases  in  which  cyanosis  was  the  only  untoward  symptom  observed 
were  included  in  this  report,  inasmuch  as  the  cyanosis  was  an  iine.K- 
jH'cted  and  undesired  efl'eel  of  (he  ingest  ion  of  (he  diiig  in  each  case 
and  u  manifestation  of  its  harmful  <iualities. 


22 


ACETANILID,    ANTIPYRIN,    AND   PHENACETIN. 


The  total  number  of  cases  of  poisoning  herein  described  is  297  or 
more,  reported  by  177  observers.  The  exact  number  of  cases  can  not 
be  determined  with  accuracy,  inasmuch  as  some  of  the  authors  refer 
to  the  number  of  cases  observed  by  them  under  such  indefinite  terms 
as  "  several,"  "  many,"  "  a  few,"  etc.  The  number  of  cases  reported 
for  each  year  is  set  forth  in  the  following  table : 

Cases  of  acetanilid  'poisoning  recorded,  1886-1907. 


Year. 

Number 
of  cases. 

Percent- 
age of 
total 
number 
of  cases 
by  the 
three 
agents. 

Year. 

Number 
of  cases. 

Percent- 
age of 
total 

number 

of  cases 
by  the 
three 

agents. 

1886 

20 
94 

21 
23 
27 
9 
5 
5 
7 
6 

20 
4 

6.7 
31.  5 
7.0 
7.7 
9.0 
8.0 
1.6 
1.6 
2.3 
2.0 
6.7 
1.3 

1898 

3 

2 
2 
6 
2 
4 
1 
9 
19 
8 

1.0 

1887 

1893 

.6 

1888 

1900 

.6 

1889 

1901 

2.0 

1890                                  

1902 

.6 

1891 

1903 

1.3 

1892 

1904 

.3 

ISVi 

190.5 

3.0 

1894 

190() 

6.3 

1895 

1907 

2.6 

Total 

1897 

297 

Of  the  total  number  of  cases  recorded,  114,  or  more  than  one-third 
(38  per  cent),  were  reported  during  the  year  and  a  half  following 
the  advent  of  acetanilid  as  a  medicinal  agent  in  August,  1880,  and 
185,  or  more  than  one-half  (62.2  per  cent),  were  reported  during  the 
first  four  and  a  half  years  of  its  history.  The  occurrence  of  so  large 
a  proportion  of  the  cases  during  this  period  was  undoubtedly  due  in 
part  to  the  fact  that  at  this  time  the  toxic  jDroperties  of  acetanilid 
were  not  understood  and  its  possibilities  for  harm  were  not  known  or 
appreciated.  This  is  shown  by  the  fact  that  it  was  at  first  used  almost 
entirely  as  an  antipyretic  in  febrile  diseases  and  Avas  administered 
rather  freely  to  sthenic  and  asthenic  patients  alike,  to  those  suffer- 
ing from  debilitating  diseases  like  typhoid  fever,  as  well  as  to  robust 
patients  suffering  merely  from  minor  aches  or  pains.  The  results  of 
this  free  administration  were  disastrous,  and  the  number  of  instances 
in  which  death  was  hastened  by  ill-advised  use  of  acetanilid  during 
the  early  years  of  its  history  can  only  be  surmised.  After  the  drug 
had  been  more  thoroughly  studied,  however,  and  after  its  injurious 
effects  in  many  cases  had  been  brought  to  the  attention  of  the  pro- 
fession, partly  through  personal  experience  and  partly  through  re- 
ports published  in  the  medical  press,  its  possibilities  for  harm  came 
to  be  more  fully  appreciated  and  it  was  used  more  and  more  con- 
servatively, particularly  in  asthenic  cases.  As  a  result,  the  number 
of  cases  of  poisoning  fell  off  rapidly  and  during  the  thirteen  years 


LITERATURE    ON    ACETANILID    POISONING. 


23 


following  1801  the  number  averaged  but  six  annually.  Since  the 
year  lOO-t,  however,  there  has  been  a  notable  increase  in  the  number 
of  cases  reported  as  well  as  in  the  number  of  fatalities.  This  can  l)e 
adequately  explained  by  the  fact  that  during  recent  j-ears  the  control 
of  acetanilid  as  a  remedial  agent  has  rapidly  passed  from  the  hands 
of  the  medical  profession  to  those  of  the  laity,  owing  largely  to  the 
advertising  efforts  of  the  manufacturers  of  proprietary  medicines, 
and  the  increase  in  the  number  of  cases  reported  and  in  the  number  of 
fatalities  is  imdoubtedl}^  mainly  due  to  the  ill-advised  and  promiscu- 
ous use  of  acetanilid  preparations  by  the  laity  for  the  relief  of 
headache  and  other  minor  ills. 

Of  the  297  cases  reported,  13,  or  4.3  per  cent,  terminated  fatally. 
The  number  of  deaths  occurring  each  year  is  set  forth  in  the  follow- 
ing table. 

Fatdl  rases  of  acctaniUd  poisoning,  JHSG-lUOl. 

(No  casps  rcportod  for  the  years  omitted.] 


Year. 


1S87 
l.SXH 
1890 
1891 
1890 
1898 


Percent- 

Number 

age  of 

of  fatal 

totjil 

cases  re- 

n  limber 

I)orterl. 

of  fatal 

cases. 

1 

7.fi  * 

1 

7.<) 

1 

7.IJ 

1 

7.6 

2 

\h.-l 

1 

7.  (J 

Year. 


1905 

I'JUtt 

iyo7 

Total 


Number 
of  fatal 
case.s  re- 
ported. 


Percent- 
age of 
total 
number 
of  fatal 
cases. 


7.0 
15.2 
22.8 


It  is  interesting  to  note  that  although  185,  or  02.2  per  cent,  of  all 
the  cases  were  reported  during  the  first  four  and  one-half  years  of  the 
hi.story  of  acetanilid  as  a  medicine,  the  number  of  deaths  from  acet- 
anilid poisoning  which  occurred  during  this  time  was  only  3  or  l.G 
per  cent;  whereas  during  the  last  three  years,  since  the  drug  has  been 
used  more  or  less  indi.scriminately  by  the  public,  the  percentage  of 
fatalities  reported  has  been  lO.G  per  cent. 

In  20,  oi-  8.7  per  cent,  of  the  cases  reported,  poisoning  I'esiiilcd  IVoin 
external  application.  These  cases  are  of  particular  interest  as  they 
afford  an  illustration  of  the  toxic  power  of  acetanilid.  In  one  of 
these  cases  the  [misoning  resulted  fatally."  The  following  abstract 
tal«Mi  fiom  a  report  by  (iartmaii  and  liall  in  1S1)7 ''  gives  an  iiliisti-a- 
lion  of  tlie  clinical  i)icture  in  this  class  of  ca.ses: 

f'liild.  ?,l  yffirs  old.  A  scii  Mr-d  !ir<';i  of  skin  was  drosscnl  willi  llircc  oniK-cs  nf 
a  10  |ior  <-(Mif  oiiitiiu'iif  of  iicctaiiilid.  Two  days  later  llm'c  oiiiK-fs  wcro  .i^'aiii 
ajjpllod,  and  the  child  bejiaii  t<»  tnni  blue.  Tbo  cyanosiB  deepened  until  tin; 
skill  and  viHi!)lo  iiiiK-fMiH  incnibranes  wtTo  of  a  blacklsli-bliie  color,  and  syinptoni.s 


n  Itftok,  ('.  W      I'olsfudnK  l».v  iicctanilld.     J.  Anicr.  Med.  .\hsii..  ISilC,  20:  2.">n. 
''A  CISC  of  ;i(<-l:iiiiiid  poisoning.     I'Jiil.idclplii.i   I'olyi-lynic,  1S!)7,  <>:  IWl. 


24 


ACETANILID,    ANTIPYRIN,    AND    PHENACETIN. 


of  collapse  appeared.     The  ointuieot  was  discontinued  and  the  symptoms  gradu- 
ally disappeared. 

The  symptom  which  appears  most  frequently  in  the  recorded  cases 
of  poisoning  by  acetanilid  is  cyanosis.  With  but  very  few  exceptions 
it  is  a  constant  symptom,  the  depth  of  the  discoloration  ranging  from 
a  mere  dusky  hue  of  the  skin  or  mucous  membrane  to  a  color  which 
is  described  as  "  blackish-blue  "  or  even  "  black."  This  symptom  was 
observed  from  the  first  and  even  in  Cahn  and  Hepp's  original  article, 
which  marked  the  advent  of  acetanilid  in  the  world  of  medicine, 
cyanosis  is  casually  mentioned  as  a  side  effect  of  the  administration 
of  the  drug.  At  that  time  but  little  significance  was  attached  to  its 
occurrence.  We  now  know,  however,  that  it  is  an  exceedingly  un- 
desirable symptom,  inasmuch  as  it  is  due  to  a  deterioration  in  the 
quality  of  the  blood  caused  directly  by  the  presence  of  decomposition 
products  of  acetanilid.  Accompanying  the  cyanosis  there  was  ob- 
served in  most  of  the  cases  prostration,  which  varied  in  degree  from 
mere  depression  of  the  bodily  functions  to  actual  collapse. 

In  addition  to  these  symptoms  there  w^ere  obserA^ed  in  many 
instances  vertigo,  faintness,  liviclity  of  the  face,  a  pinched  and 
anxious  expression,  dyspnea,  excessive  restlessness,  increased  perspi- 
ration, coldness  of  the  extremities,  rapid  and  feeble  heart  action,  and 
in  severe  cases,  stupor  or  coma.  The  occurrence  of  an  eruption  on 
the  skin  is  mentioned  in  only  a  very  few  of  the  recorded  cases.  This 
is  also  true  of  disturbances  of  vision  and  of  the  functions  of  the 
kidneys. 

The  habitual  use  of  acetanilid  is  specifically  mentioned  in  32,  or  10.7 
per  cent,  of  the  recorded  cases  of  poisoning.  This  gives  no  conclu- 
sive information,  however,  as  to  the  actual  extent  of  the  acetanilid 
habit,  inasmuch  as  only  those  instances  of  habitual  use  are  recorded 
in  which  the  ill  effects  were  probably  so  severe  as  to  cause  the  patient 
to  seek  the  advice  of  a  physician.  A  consideration  of  the  relative 
number  of  cases  occurring  in  different  years  is  of  value,  however, 
and  shows  a  marked  increase  in  the  number  of  cases  of  habitual  use 
during  recent  years,  as  indicated  in  the  following  table : 

Cases-  of  hahitual  use  of  acetanilid  reported,  1800-1907. 
[No  cases  roported  for  the  years  omitted.] 


Year. 


1890 
1S94 
1896 
1899 
1900 
1902 


Percent- 

age of  to- 

Number 

tal  num- 

of cases 

ber  of 

reported. 

cases  of 

habitual 

use. 

1 

3.12 

2 

6.24 

2 

6.24 

1 

3.12 

1 

3.12 

1 

3.12 

Year. 


1903 

1905 

1906 

1907 

Total 


Number 
of  cases 
reported. 


Percent- 
age of  to- 
tal num- 
ber of 
cases  of 
habitual 


12.50 
15.60 
40.62 
6.24 


LITERATURE    ON    ACETANILID    POISONING. 


25 


The  increasing  u.se  of  proprietary  remedies  containing  acetanilid 
since  the  year  1001  is  indicated  in  the  published  reports,  as  follows: 

Cases  in  irhicli  the  patient  is  reported  to  have  taken  a  proprietary  preparation, 

1891-1907. 

[No  cases  reported  for  the  years  omitted.] 


Year. 

Number 
of  cases 
reported. 

1 
1 
3 

Percent- 
age for 
each 
year. 

Year. 

Number 
of  cases 
reported. 

Percent- 
age for 
each 
year. 

1891 

3.7 
3.4 
10.3 
17.2 

1906 

12 

7 

41.3 

1895 

1907 

24.1 

1896 

Total 

1905 

29  ' 

The  use  of  proprietary  preparations  containing  acetanilid  is  not 
mentioned  in  the  reports  of  cases  published  during  the  eight  years 
preceding  the  year  1905,  but  in  the  reports  published  during  1905 
the  use  of  these  preparations  is  indicated  in  55.5  per  cent  of  cases. 
In  1906  the  use  of  these  preparations  is  indicated  in  63.1  per  cent  of 
the  recorded  cases,  and  in  1907  in  87.5  per  cent.  It  is  interesting  to 
note  that  accompanying  this  rapid  increase  in  the  use  of  proprietary 
acetanilid  preparations  during  recent  years,  which  indicates  a  more 
indiscriminate  use  of  acetanilid  by  the  general  public,  there  has  been 
an  increase  in  the  total  number  of  cases  of  poisoning  reported,  in  the 
number  of  fatalities,  and  in  the  number  of  instances  of  habitual  use. 
In  this  connection  a  comparison  of  the  four  preceding  tables  is  of 
interest. 

ABSTRACTS    OF   ACETANILID    CASES. 


188G. 

Bebnheim.    L'antifi'brini'.     Kov.  iiu'-d.  de  Test,  Nancy,  ISSG,  18:  099. 

Oiic-lialf  of  the  patients  takinfx  acetanilid  liad  cyanosis  of  the  face  and 
extremities;  .'j.Tn  j^raius  ^civen  to  a  child  prodnced  chills  and  collapse. 
Three  patients  had  a  chill  when  the  tcniporatnre  he^'an  to  rise  a.i,'aiii. 

Cahn,    a.,    nnd    IIum'.    ]'.     Das    Antifclirin,    ein    nenes    Fichci-iiiillcl.     Centrlil. 
kiln.  .Med.,  Leipzif,',  ISSO,  7:  HCl. 

Cyanosis  of  the  face  and  extremities,  varying;  in  intensity,  was  tiie  only 
perplexing;  symptoiu  observed  dnrin^x  tlie  adniinisti'al  ion  r)f  acetanilid. 

i:iSKMi,\i!T.  n.     I',eohii(litnn;.'cii  iiher  das  Antifclirin.     .Miincli.  mod.  Wdclicnsclir., 
ISSO,  »:{:  S.-.I. 

Itifreslion  of  acetanilid  was  followed  by  the  ;ippear:ince  of  a  paiinlar 
ernption  coverinK  tlie  etitin;  l)ody. 

Kkik<.i,I'..   ('•.     Antifebrin    ( Acelanilin  )    als   Antifebrile   nnd    Aid  iseptii-nni.     Cen- 
trl»l.  lilin.  M(!d.,  Leip/JK,  bSStJ,  7:  7<;]. 

Cyanosis  of  tlje  dieeivS  and  visible  inncons  nicinbranes  was  the  only  ill 
effect  obHerved  durhig  the  administratir)n  of  acetanilid. 


26  ACETANILID,   ANTIPYRIN,    AND    PHENACETIN. 

Lepine,  R.     Sur  I'action  cle  I'acetanilide    (autifebrine).     Semaine  nied.,   Paris, 
1886,'  6:  473. 

Doses  of  more  than  7.5  grains  of  acetanilicl,  continued  for  several  days, 
caused  cyanosis  of  tlie  face  and  extremities. 

MouissET.     Note  sur  Temploi  de  I'acetanilide  dans  le  traitement  de  la  fievre 
typhoide.     Lyon  med.,  1886,  53:  309. 

Three  out  of  seven  cases  of  typhoid,  treated  with  acetanilid  in  doses  of 
7.5  grains,  presented  symptoms  of  cyanosis. 

RiESE,  H.     Zur  Wirkung  des  Antifebrin.     Deutsche  med.  Wochenschr.,  Berlin, 

1886,  12:  835. 

Cyanosis  of  the  face  and  extremities  appeared  in  several  cases,  particu- 
larly in  phthisis,  following  the  use  of  acetanilid.  In  two  cases  of  pneu- 
monia and  one  of  typhoid  the  pulse  became  weak  and  irregular.  Collapse 
occurred  after  a  single  dose  of  11.5  grains  of  acetanilid  in  a  case  of  phthisis. 

1887'. 

Bauer,   F.  M.     The  dangers  of  antifebrin.     Therap.    Gaz.,   Detroit,   1887    (3), 
3:  788. 

Author  had  several  times  seen  cyanosis  produced  in  women  by  three  or 
four  doses  of  3.75  grains  of  acetanilid. 

Biro,  E.     Az  acetanilid    (antifebrin)    hatasarol.     Gyogyaszat,   Budapest,   1887, 
27:  217.     (Transl.  Abs.,  Pest,  med.-chir.  Presse,  Budapest,  1887,  23:  446.) 

(1)  Ingestion  of  7.5  grains  of  acetanilid  was  followed  by  a  severe  rigor 
and  an  irregular,  small  pulse.  (2)  After  'taking  acetanilid  for  eleven 
days  the  patient  presented  the  same  symptoms  as  in  case  1,  and,  in  addition, 
clonic  convulsions  of  the  lower  extremities. 

BoROSNYoi,  L.     Az  antifebrin  mint  eskorellenes  szer.     Orvosi  hetil.,  Budapest, 

1887,  31:  1663.      (Transl.  Abs.,   Pest,   med.-chir,    Presse,    Budapest,    1888, 
24:  103.) 

Author  observed  cyanosis  in  all  cases  of  epilepsy  treated  with  large  doses 
of  acetanilid. 

BouLTON,  p.     Antifebrin.     Brit.  Med.  J.,  London,  1887,  1 :  761. 

On  two  occasions  marked  prostration  followed  the  administration  of  15- 
grain  doses  of  acetanilid  to  feeble  patients. 

Cauldwell,  C.  M.     Antifebrin  in  the  treatment  of  phthisis.     Med.  Rec.    New 
York,  1887,  31:  426. 

Cyanosis  of  the  lips  and  finger  nails  was  noted  in  2  cases  out  of  30 
treated  with  acetanilid,  in  7  to  ]0-grain  doses. 

Demikville,  p.     De  I'antifebrine  comme  nervin.     Rev.  med.  de  la  Suisse  Rom 
Geneve,  1887,  7:  305. 

(1)  In  an  alcoholic  epileptic,  51  years  of  age,  7.5  grains  of  acetanilid 
three  or  four  times  a  day  caused  delirium  and  hallucinations.  (2)  Several 
15-grain  doses  of  acetanilid  caused  lachrymation  and  a  prickling  sensation 
about  the  eyes. 

Doll.     Mittheilungen  aus  der  Praxis.     Deutsche  Med.-Ztg.,  Berlin,  1887,  8:  817. 
Ingestion  of  25  pfennigs'  worth  of  acetanilid,  about  1.5  tablespoonfnls, 
in  two  portions  in  close  succession  was  followed  in  about  three  hours  by 
vomiting,  syncope,  and  collapse. 


LITERATURE    ON    ACETANILID   POISONING,  27 

DrJARDiN-REArMETZ.  De  racvtanilide  conime  niMicniiuMit  sedatif  (In  systOine 
nerveiix.     Bill.  gen.  tberai).  (etc.),  Paris,  1887,  112:  241. 

Antlior  had  observed  cyanosis  following  the  administration  of  doses  of 
7.5  grains  of  acetauilid  in  febrile  cases,  particularly  in  typhoid. 

DuLACSKA,  G.  Az  acetanilid  hatasarol.  Gyogytiszat,  Budapest,  1887,  27:  103. 
Transl.  Abs.,  Pest,  med.-chir.  Presse,  Budapest,  1887,  23:  444. 

Two  .3-grain  doses  of  acetanilid  at  two-hour  intervals  caused  epistaxis 
in  one  case  and  profuse  uterine  hemorrhage  in  another.  After  taking 
acetanilid  a  phthisic:)]  patient  became  drowsy  and  the  lips  showed  moderate 
cyanosis.  In  all  cases  the  ingestion  of  the  drug  was  followed  by  marked 
prostration. 

Editorial.  Antipyrin  and  antifebrin.  New  Orleans  Med.  and  Surg.  J.,  1887, 
15  (1)  :  50. 

A  patient  with  remittent  fever  took  7.5  grains  of  acetanilid  every  hour 
until  0.5  drachm  was  taken.  The  temjierature  fell  to  95°  and  the  patient 
became  almost  pulseless. 

EiSExnART.  II.  Beoliachtungen  fiber  das  Antifebrin.  Miinch.  mod.  Wochenschr., 
1887,  U:  448. 

A  1.5-grain  dose  of  acetanilid  produced  cyanosis,  and  smaller  doses  caused 
a  mild  bluish  discoloration  of  the  face.  The  ingestion  of  4  drachms  of  acet- 
anilid within  six  days  in  a  case  of  rheumatism  was  followed  by  the  develop- 
ment of  a  morbilliform  eruption. 

Faube,  .J.  L.  Notes  sur  les  effets  de  Tacetanilide  dans  le  traitement  de 
"epilepsia.     Compt.  rend.  soc.  biol.,  Paris,  1887  (8),  4:  401. 

The  administration  of  from  7.5  to  37.5  grains  of  acetanilid  daily  caused 
well-marked  cyanosis. 

Fattst,  W.  rel)er  Antifebrin.  Deutsche  med.  Wochenschr.,  IjCipzig  and  Ber- 
lin, 18S7,  13:  358. 

Two  doses  of  7.5  grains  of  acetanilid  reduced  the  temi^erature  to  94.2° 
without'symptoms  of  collapse. 

Fischer,  (i.  Antifebrin  gegen  lancinirende  Schmerzen.  IMiinch.  med. 
Wochenschr.,  1SS7,  34:  42.'"). 

In  2  c.-ises  out  of  10  cyanosis  followed  the  admiMislraUon  of  7.5  to  22.5 
grains  of  acetanilid. 

(Jor.orsriiEW.  Discussion  of  paper  liy  Ansserow  on  "Antifebrin.  Antipyrin, 
mid  'I'liallin  a  is  Mittel  ziir  Keguiining  des  Wiii-iiievcilnstt's  lie!  Fiebernden." 
Deuts<-be  med.-Ztg..  P.erlin,   1.S.S7.  H:  2;{4. 

Ingestion  of  4.5  grains  of  acetiiiiilid  caused  collaijse. 

GiTTMANN.  (i.  Antifebrin.  in  seine?'  iiiannigfaltigen  \VirI<uiigsweis(>.  I'.ei'l. 
kiin.  Wochenschr.,  1SS7.  24:  942. 

Ill  4  nut  of  248  cases  lln'  ingcslioii  of  acetanilid  was  fr)llowed  by  cyanosis 
of  the  lips  and  cheeks,  (lis.ippe.iriiig  within  an  Iioiir. 

IIaims.  C.     Antifebrin.  P.rit.  Med.  .].,  [.oiidon,  1.SS7.   1:   12.5.3. 

The  adiiiiiiistr'atioii  (if  I  grains  of  .'icet;milld  (o  :i  sen riel- fever  palieiil  S 
years  of  age   was   followed    by   a    rapid    fall    nf   lem|ier;it  iire   and    coll.ipse. 


28  ACETANILID,   ANTIPYEIN,   AND   PHENACETIN. 

Heinzelmann,  H.  Zur  Casiiistik  der  Antifebrinbehandlung,  Munch,  med. 
Wocheusclir.,  1SS7,  34:  36. 

Ingestion  of  3.75  grains  of  acetanilid  was  followed  in  one  case  by  dilation 
of  tlie  pupils,  in  another  by  chilliness  and  profuse  perspiration,  and  in  still 
another  by  weakness  of  the  pulse.  In  a  fourth  case  partial  deafness  and 
headache  followed  the  ingestion  of  7.5  grains  of  the  drug. 

Heusler,  E.     Das  Antifebrin.     Allg.   med.   Centr.-Ztg.,   Berlin,   1887,   56:1074. 
In  50  cases  of  typhoid  and  pneumonia  treated  with  acetanilid,  cyanosis 
occurred  in  one  instance.     Average  dose,  3.75  grains  every  six  hours. 

HuBER,  A.     Ueber  Antifebrin.     Cor.-Bl.  f.  schweiz.  Aerzte,  Basel,  1887,  17:2. 
Typhoid.     Ingestion  of  7.5  grains  of  acetanilid  daily  for  two  days  was 
followed  by  a  papular  rash  especially  marked  on  the  forehead,  forearms, 
and  hands.     Author  had  also  observed  instances  in  which  cyanosis  and  col- 
lapse followed  the  ingestion  of  acetanilid. 

Jacob,  A.     Etude  cliuique  sur  I'antifebrine  on  acetanilide.     Nancy,  1887. 

In  72  cases,  cyanosis  was  observed  in  12  instances  following  the  ingestion 
of  3.75  to  7.5  grains  of  acetanilid.  Collapse  occurred  in  2  instances  after 
the  ingestion  of  acetanilid  by  typhoid-fever  patieuts ;  once  after  the  ad- 
ministration of  7.5  grains,  and  again  after  3.75  grains.  In  a  case  of  hemi- 
plegia, a  dose  of  half  a  drachm  was  followed  by  intoxication  and  nausea 
lasting  four  hours.  Three  and  three-fourths  grains  produced  syncope  in 
case  of  a  tubercular  patient. 

JuNKERMANN,  F.  A.     Antifebrin  als  Febrifugum  und  Nervinum.     Wiirzburg, 

1887. 

In  erysipelas,  cyanosis  was  observed  to  follow  the  ingestion  of  doses  of  7.5 
grains  of  acetanilid. 

MacMullen.  J.  C.  On  the  action  of  acetanilide.  Australas.  INIed.  Gaz., 
Sydney,  1886-7,  6:269. 

In  at  least  three  cases,  a  condition  closely  resembling  collapse  followed 
the  ingestion  of  acetanilid. 

Matusofszky,  A.  ITeber  den  Heilwert  des  Antifebrin.  Orvos-termeszettud. 
Ertesito.  Kolozsvar,  1887.  No.  1.  (Transl.  Abs.,  Pest,  med.-chir.  Presse, 
Budapest,  1887,  23:  466.) 

(1)  Cyanosis  occurred  in  a  case  of  phthisis  after  the  ingestion  of  0.75 
grain  of  acetanilid  four  to  five  times  a  day.  (2)  Typhoid.  Four  doses  of 
acetanilid,  6  grains  each,  every  half  hour  causes  cyanosis  and  collapse. 

MiJLLER,  J.  Meeting  of  Soc.  de  med.  de  Strasbourg,  Jan.  0,  1887.  Gaz.  med.  de 
Strasbourg,  1887,  46:  35. 

Administration  of  7.5  grains  of  acetanilid  to  a  patient  with  erysipelas 
9  years  of  age  caused  intense  cyanosis  of  the  face. 

Pavai-Vajna,  G.  Ueber  die  Wirkung  des  Acetanilid  Oder  Antifebrin.  Centrbl. 
gesam.  Therap.,  Wien,  1887,  5:  481. 

(1)  Man,  25,  phthisis:  Fifteen  grains  of  acetanilid  caused  cyanosis  and 
collapse.  (2)  Man,  28,  typhoid:  Three  and  three-fourths  grains  caused 
cyanosis.  (3)  Man,  27,  pneumonia :  Three  doses  of  3.75  grains  at  hourly 
intervals  caused  profuse  perspiration  and  cyanosis. 


LITERATURE   ON   ACETANILID   POISONING.  29 

Salm,  a.  I'eber  Autifebriu  a  Is  Antiepilepticum.  Neurol.  Ceutrbl.  Leipzig, 
1887,  6:  241. 

Nearly  all  of  11  epileptic  patients  treated  with  acetanilid,  15  to  45  grains 
a  day,  presented  cyanosis  and  a  dark  discoloration  of  the  urine. 

ScHTscHERBAKow.  I'ebcr  den  Gebranch  von  Antifebrin  und  Naphtha  bei 
Schwindsiichtigen.   Deutsche  med.  Ztg.,  Berlin,  1887,  8:  234. 

Acetanilid  given  by  inhalation  produced  collapse  in  several  cases. 

Secbetan,  L.  Note  sur  I'antifebrine.  Rev.  med.  de  la  Suisse  Rom.,  Geneve, 
1887,  7:  36. 

(1)  Rheumatism:  Collapse  followed  the  second  dose  of  7.5  grains  of 
acetanilid.  (2)  Tuberculosis:  Collapse  followed  a  single  dose  of  7.5  grains 
of  acetanilid. 

Seiffp^jt.  E.  V.  A.  leiter  Antifebrin  und  seine  Anwendung  beim  akuten  Gelenk- 
rheumatisnui.s.     Berlin,  1887. 

Youth.  IS:  Ingestion  of  7.5  grains  of  acetanilid  four  times  a  day  for  two 
days  was  followed  by  cyanosis. 

Sexton.  J.  C.  Acetanilid  "Antifebrine."  Cincinnati,  Lancet  Clinic,  1887  (n.  s.), 
19:  184. 

Acute  miliary  tul)erculosis.  The  ingestion  of  15  grains  of  acetanilid 
was  followed  by  cyanosis  and  collapse. 

SipPEL.  H.  I'eber  Antifebrinboliandlnng.  Miinch.  med.  Wochenschr.,  1887,  3-t: 
215. 

(1)  Three  and  three-fourths  grains  of  acetanilid  caused  severe  itching 
•»f  skin.  (2)  Ingestion  of  about  TOO  grains  of  acetanilid  within  five  days 
by  a  phthisical  patient  was  followed  by  nausea,  dizziness,  buzzing  in  the 
ears,  and  cyanosis.     In  one  patient  3.75  grains  produced  partial  deafness. 

'I'RosT,  J.  A.     Antifebrin.     Kansas  City  Med.  Index,  1887,  8:  228. 

Remittent  fever.  Acetanilid,  8  grains  every  six  hours,  at  end  of  third 
day  caused  cyanosis  and  collapse. 

Trussewitsch.  Discus,  of  Ansserow :  Vergleicluing  der,  die  Wiirmeverluste 
ausgleiclicndtMi.  Wii'kung  des  Antifebrin  in  riehernden  Organisnien  mil  der 
des  Antiityrin  und  Tluillin.  Congress  russ.  Aerzte  zu  .Moskau.  Therap. 
Mouatsh.,  Berlin,  1887,  1:  107. 

Seven  and  one-half  grains  of  acetanilid  caused  collapse  in  a  typhoid 
fever  patient  13  years  of  age. 

ViNEfsERc;,  II.  .\.  A  caution  in  regard  to  acetanilide.  New  York  Med.  J.,  1887, 
40:  21  !i. 

A  tji)hoid  fever  jtatient  was  given  10  grains  of  acetanilid  every  four 
hours.    After  0  doses  marked  cyanosis. api)eared,  with  symptoms  of  collaj)s('. 

\o.N  QuAST,  E.  A  death  frrtm  antifebrin.  (Note  by  editor  of  Index.)  Kansas 
(  Ity  Med.  Index,  1887,  8:  229. 

The  administration  of  4  grains  of  acetanilid  every  two  hours  <luring  the 
day  to  a  cjiild  was  followed  by  cyanosis.  collai)se.  and  death. 

Weii.i,.  I»e  Taction  jdiysiologiipie  et  tlicraiieutMiuc  de  ra(/'lanilide.  Bui.  gen. 
therap.,  etc.,  I'arls,  1887,  112:  150. 

Seven  and  oue-half  grains  of  acetanilid  prodiKcd  cyanosis  in  a  case  of 
typhoid. 


30  ACETANILID,    ANTIPYRIN,    AND   PHENACETIN. 

Weinstein,  N.  Ueber  Calomel- Autifebriu-Kawa.  Wieu.  med.  Bl.,  1S87,  10:  305, 
340. 

(1)  Seven  and  one-half  grains  of  acetanilid  produced  cyanosis  of  the 
face  in  a  woman  22  years  of  age,  with  puerperal  fever.  (2)  The  same 
dose  caused  marked  cyanosis  in  a  woman  43  years  old,  with  erysipelas. 

WiDOWiTz,  J.  Antifebrin  bei  fieberhaften  Erkrankungen  der  Kinder.  Wien. 
med.  Wochenschr.,  1887,  37:  572. 

Boy,  12,  pneumonia :  Intense  cyanosis  of  the  face  and  finger  tips  fol- 
lowed the  ingestion  of  each  dose  of  3  grains  of  acetanilid. 

WiNNETT,  H.  J.     Was  it  antifebrin?     Therap.  Gaz.,  Detroit,  1887  (3),  3:  646. 

Five  grains  of  acetanilid  every  four  hours  were  ordered  for  tonsilitis. 
After  3  doses  had  been  taken  there  appeared  marked  cyanosis  with  rapid 
and  feeble  pulse. 

18W8. 

Apotheker  Ztg.,  1888.  Poisoning  by  uutifebrine.  Abs.  in  Med.  News,  Phila- 
delphia, 1889,  54:  45. 

Ingestion  of  0.5  drachm  of  acetanilid  twice  in  twenty-four  hours  was 
followed  by  cyanosis,  anxiety,  cold  perspiration,  and  great  depression. 

Bkingiee,  J.  T.     Antifebrine.     Med.  World,  Philadelphia,  1888,  6:  377. 

In  typhoid  acetanilid  in  4-grain  doses  caused  copious  sweating,  depression 
of  the  heart,  thoracic  oppression.  The  rise  in  temperature  was  in  every 
case  accompanied  by  coldness  of  the  extremities. 

Demme,  R.  Ueber  die  Anwendung  und  Wirkung  des  Salols,  Antifebrius,  und 
Urethans  im  Kindesalter.  Abs.  in  Internat.  klin.  Rundschau,  Wien,  1888, 
2:  lis. 

Boy,  11,  phthisis :  One  and  one-half  grains  of  acetanilid  five  times  a  day 
causes  cyanosis.  Acetanilid  produced  profuse  diarrhea,  and  nausea  in  a 
girl  and  a  boy  suffering  from  erysipelas. 

Tkeund,  C.  S.  Ein  Fall  von  Antifebrinvergiftung.  Deutsche  med.  Wochenschr., 
Leipzig,  1888,  14:  834. 

Man,  29:  Took  45  grains  of  acetanilid  at  11  a.  m.  and  again  at  2  p.  m. 
By  5.30  p.  m.  he  was  deeply  cyanotic  and  his  pulse  had  increased  in 
rapidity  to  152.     Cyanosis  lasted  about  four  days. 

Hardy.     Brit.  Med.  J.,  London,  1888,  1:  661. 

Report  of  a  case  in  which  sudden  death  followed  the  eighth  administra- 
tion of  a  15-grain  dose  of  acetanilid. 

Klippel,  C.  Antifebrin — Its  value  as  a  therapeutic  agent.  Kansas  City  Med. 
Rec,  1888,  5:  441. 

(1)  Woman,  age  21,  acute  metritis:  Three  4-grain  doses  of  acetanilid  at 
intervals  of  three  hours  caused  cj^anosis  and  dyspnea ;  3-grain  doses  subse- 
quently gave  similar  symptoms.  (2)  In  two  other  cases  the  symptoms  were 
like  those  mentioned  above,  but  not  so  marked. 

Keonecker.  Einige  Beobachtungen  iiber  die  Neben-Wirkungen  des  Antifebrius. 
Therap.  Monatsh.,  Berlin,  1888,  2:  426. 

Youth,  18,  typhoid:  Profuse  perspiration  and  collapse,  passing  into  coma, 
followed  the  administration  of  3  grains  of  acetanilid. 


LITERATURE   ON   ACETANILID   POISONING.  31 

LowENTHAL,  L.     Zur  Wirkims  des  Antifebriu.     Tlienu).  Moiiatsli.,  Berlin,  1S88, 
2:  428. 

Child,  1  year  ()1(1.  piuniiiKiiiia  :  Tliree-f(»nrtlis  of  a  irrain  of  afetaiiilid 
caused  severe  collapse.  Aft»'r  four  Lours  tlie  teiiiperalure  rose  rapidly. 
There  was  a   letaiiic  spasm   lastin.iL;  for  half  a  minute. 

Meekel,  G.      (  Ilandverkauf  des  Antifebriu.)      Miiucli.  lued.   Woehenscbr.,  1888, 
35:  899. 

(1)  Ingestion  of  ten  powders,  each  containing  7.5  grains  of  acetanilid, 
was  followed  by  severe  eollaiise,  the  patient's  life  being  saved  with  diffi- 
culty. (2)  Collapse  followed  the  ingestion  of  1.5  drachms  of  acetanilid 
taken  in  divided  doses  at  frequent  intervals. 

Meylr,  .1.     Antifebriu-^'ergiftuug.     Therap.  Monatsh.,  P.eriiu,  1888,  2:  p.  259. 

Man.  :;8 :  lugestitm  of  30  grains  of  acetauilid  was  followed  by  cold  sweat, 
dizziness,  and  headache;  cyanosis  of  the  face  and  mucous  membranes,  and 
rapid  and  feeble  pulse. 

ScHAPEn.     Ueber  Antifebriu.     Deutsche  Mil.-iirztl.  Zts.,  r.erlin,  1888,  17:  KiO. 
In   typhoid,   7.5  grain  doses  of  acetanilid    (45  grains   in  twelve  hours) 
produced      well-marked      cyanosis.     In      pneumonia,      acetanilid      caused 
cyanosis. 

VoLK.     :Miinch.  med.  Wochenschr.,  1888,  35:  819. 

After  taking  several  doses  of  acetanilid  frt)m  the  end  of  a  knife  blade 
the  patient,  a  man,  became  deeply  cyanosed,  and  passed  into  a  condition 
of  collapse  and  weakness  which  lasted  for  several  days. 

Von  HoBMANN.    Autifebriu-Intoxicatiou.    Vereinsbl.  pfiilz.    Aerzte,  1 888,  4 :  18S. 
Ingestion  of  about  0.5  drachm  of  acetanilid  by  a  woman  was  followed 
by  deep  cyanosis. 

18S9. 

Aliscii.     T'eber  einen  Fall  von  Antifebrinvergiftung.     Therap.  Monatsh.,  Berlin, 
1889,  3:  340. 

Man  took  three  doses  of  acetanilid  of  3.75  grains  each  at  hourly  intervals. 
This  was  followed  by  a  severe  headache  and  dizziness,  and  later  a  chill, 
cyanosis,  clonic  contractions  of  the  muscles,  and  rapid,  feeble  pulse. 

.Vllison,   W.    R.     a    case   of   poisoning   by    antifebriu.     J.    Auiei-.    Med.    Assn., 
Chicago,  1889,  12:  103. 

Man  took  l)y  mistake  at  5  a.  m.  about  17  fluid  drachms  of  a  mixture 
containing  1  ounce  (if  acetanilid  to  0  ounces  of  comi)ound  elixir  of 
taraxacum.  In  thirty  minulcs  there  was  intoxication  and  desire  to  sleep. 
Slept  until  10  o'clo<k.  At  3  p.  m.  he  sought  a  jdiysician,  who  found  deeii 
cyanosis,  gn^at  prostration,  giddiness,  cold  persjtiration ;  pulse  110,  respira- 
tion .30. 

Rrieoer.    I>.         KIne    Antifebriu vc-rgifluug.    Tliei'ap.      .Monatsh.,      Berlin,     1889, 
3:  .381. 

Tatient  took  15  grains  of  acetauilid,  and  in  an  hour  7.5  grains  m<»re. 
'I'his  was  followr'd  by  vomiting,  deep  cyanosis,  twitching  of  the  mu.scles, 
and  double  vision. 


32  ACETANILID,    ANTIPYRIN,    AND   PHENACETIN. 

Chakanow.  Ein  Fall  von  Vergiftnng  mittelst  Antifebriu.  St.  Petersb.  med. 
Wochensclir.,  1889,  14  (N.  F.,  6)  :  369. 

A  dose  of  15  grains  of  acetanilid  night  and  morning  was  followed  by 
cyanosis,  nausea,  wealvuess,  shivering,  and  irregular  heart  action. 

FiJRTH,  E.     Eine  Antifebrinvergiftung.     Wien.  med.  Presse,  1SS9,  30:  652. 

Sixty-two  grains  of  acetanilid  in  one  dose  caused  persistent  vomiting, 
cyanosis,  shallow  and  slow  breathing,  dilation  of  the  pupils,  great  restless- 
ness, muscular  twitching,  delirium,  and  coma. 

Gibbons,  J.  E..   Poisoning  by  antifebrin.    Maryland  Med.  J.,  1889,  21:  183. 

A  drachm  of  acetanilid  taken  in  one  dose  caused  cyanosis  and  mild  col- 
lapse. 

Greene,  W.  S.  Failure  of  antifebrin  as  an  antipyretic.  Univ.  Med.  Mag., 
Philadelphia,  1888-9,  1:  228. 

Ten  grains  of  acetanilid  seriously  affected  the  heart  iu  the  case  of  a  well- 
nourished  adult. 

Haigh,  J.  Effects  of  antifebrine  upon  memory.  Med.  World,  Philadelphia, 
1889,  7:  423. 

Report  of  two  cases  in  which  gradual  loss  of  memory  was  caused  by  the 
long  continued  administration  of  acetanilid. 

Haley,  R.     A  ca.se  of  antifebrine  poisoning.     Weekly  Med.  Rev.,  1889,  20:  371. 

Young  woman  took  4-grain  doses  of  acetanilid  frequently  for  three  days. 

On  the  third  day  she  suddenly  fell  from  the  chair  unconscious.     Could  not 

talk  at  first,  and  later  only  with  difiiculty.     The  face  was  blue,  skin  cold, 

and  there  was  much  dyspnea. 

Henschen,  S.  E.  Om  s.  k.  kontrar  verkan  af  febermedel.  TJpsala  Lakaref. 
Forh.,  1888-9  (4  s.),  24:263.  Transl.  Abs.  Schmidt's  Juhrb.,  Leipzig,  1889, 
223:  241. 

Two  cases  in  which  the  administration  of  acetanilid  in  doses  of  11.25  and 
3.75  grains,  respectively,  was  followed  by  a  rise  of  temperature  in  typhoid 
fever  patients. 

Mahnert,  F.  Ueber  Intoxicationen  mit  Antifebrin.  Memorabilien  Heilbronn, 
1889    (N.  F.),  9:  321. 

(1)  Girl,  tuberculosis:  Ingestion  of  6  grains  acetanilid  was  followed  by 
profuse  perspiration,  lividity,  and  cyanosis.  (2)  Youth,  16,  headache:  In- 
gestion of  15  grains  acetanilid  in  2  doses  with  a  half-hour  interval  was  fol- 
lowed by  cyanosis,  clammy  perspiration,  accelerated  respiration,  and  rapid 
heart  action. 

MaeIiichaux.  Ein  Fall  von  acuter  Antifebrinvergiftung.  Deutsche  med.  Woch- 
enschr.,  Leipzig,  1889,  15:  845. 

Child,  5  months  old,  was  given  3.75  grains  of  acetanilid.  In  two  and  a 
half  hours  there  was  unconsciousness,  cyanosis,  and  collapse. 

Meyer.  Fall  von  Antifebrin-Intoxication.  Allg.  Med.  Centr.-Ztg.,  Berlin,  1889, 
58:  805. 

Girl,  13,  headache:  Ingestion  of  less  than  15  grains  of  acetanilid  was 
followed  by  cyanosis  and  palpitation  of  the  heart.  On  another  occasion 
10  grains  in  2  doses,  with  an  interval  of  one  hour,  caused  similar  symptoms. 


LITERATURE   ON    ACETAXILID   POISONING.  33 

Pauschingek.     Eiu  Fall  von  Antifebrin-Vergiftung.     Miinch.  med.  Wochensclir., 
1SS9.  36:  332. 

Man,  34 :  The  ingestion  of  five  15-grain  powders  of  acetauilid  at  hourly 
intervals  caused   vertigo,  chilliness,  diarrhea,  and  cyanosis. 

Penney,  E.  W.     Antifebrin.     Times  and  Register.  Philadelphia,  1889,  20  (1)   : 
1.S3. 

Two  5-grain  doses  of  acetanilid  one  hour  apart  caused  collapse  in  a 
typhoid-fever  patient. 

Saylob,  a.   L.      Is  antifebrin   dangerous?     Times  and   Register,   Philadelphia, 
1889,  20  (1)  :  134. 

A  dose  of  4  grains  of  acetanilid  to  a  child  3  years  old  produced  symptoms 
of  collapse. 

Sembkitzki.     Zur    Wirkung   des   Antifebrin.     Therap.    Monatsh.,    Berlin,    1889, 
3:  267. 

Woman.  28,  typhoid  fever :  Administration  of  4.5  grains  of  acetanilid 
caused  severe  symptoms  of  collapse. 

Stein,   J.     Zur    Kenutniss  des  Antifebrins  und   seiner   Dosirung.     Prag.    med. 
Wochenschr..  1889.  14:  559. 

Author  observed  that  a  dose  of  1.5  grains  of  acetanilid  produced  halluci- 
nations in  the  weak  and  aged. 

Wilding.  J.     Toxic  effects  of  10  grains  of  antifebrin.     Brit.  Med.  J.,  London, 
1889,  2:  600. 

Young  man,  pulmonary  tuberculosis:  Ten  grains  of  acetanilid  caused 
collapse. 

1890. 

Armstrong,  S.  T.     A  case  of  acetanilide  poisoning.     Therap.,  Gaz.,  Detroit.  1890 
(3).  6:  245. 

Man.  28:  Took  2  drachms  of  acetanilid  in  8  powders  at  one-half  hour 
intervals  for  pain.  Although  he  vomited  freely,  there  followed  cyanosis, 
coma,  and  symptoms  of  collapse. 

BoKENHAM.  T.  .7..  and  Jones,  E.  L.     On  two  cases  of  poisoning  by  anilides  (Ex- 
algine  and  Antifebrin).    Brit.  Med.  J..  London,  1890.  1:  288. 

Woman,  43,  headache :  Ingestion  of  0.5  drachm  of  acetanilid  in  divided 
doses  within  two  and  one-half  hours  was  followed  by  headache,  symptoms 
of  intoxication,  cj-anosis,  and  unconsciousness. 

Favrat,  A.     Ueber  die  Anwendung  des  Antifebrins  in  refracto  dosi  beim  Ty- 
phus Abdominalis  und  beim  Fieber  der  Phthisiker.     (Bern)  Leipzig,  189i0. 

Doses  of  from  0.75  grain  to  1.5  grains  of  acetanilid  given  every  hour 
produced  chills  and  cyanosis  in  2  cases  of  typhoid  fever. 

f-ERBis.    A.    W.     Poisoning    with    acetanilid.     Med.    Record,    New    York,    1890, 
87:  587.  . 

Woman.  45:  Ingestion  of  15  grains  of  acetanilid  at  8  and  10..30  a.  m.  was 
followed  by  deep  cyanosis,  a  r)inclied  expression,  depressed  temi)erature,  and 
marked  prostration. 

82319— Bull.  126—09 3 


34  ACETANILID,   ANTIPYKIN,   AND   PHENACETIN. 

Hartge,  A.     Eine  Antifebrinvergiftung.     St.  Petersb.  med.  Wocliensclir.,  1890 
(N.  F.),  7:  69. 

Student  who  had  been  drinking  heavily  took  for  insomnia  teaspoonful 
doses  of  acetanilid  from  an  ounce  box  until  all  was  taken.  Symptoms  re- 
sembled those  of  anilin  poisoning.  Recovery  was  probably  due  in  part  to 
the  fact  that  the  stomach  contained  so  much  liquid. 

HattoN,  J.  B.     Some  untoward  effects  from  antifebrin.     Med.  Surg.  Reporter, 
Philadelphia,  1890,  62:  372. 

(1)  Boy,  16,  typhoid:  Administration  of  4  grains  of  acetanilid  was  fol- 
lowed by  cyanosis  and  collapse.  (2)  Man,  52,  sciatica:  Two  4-grain  doses 
of  acetanilid  four  hours  apart  caused  cyanosis  and  collapse. 

Hermann,  E.     Beobachtungen  liber  die  Wirkungen  und  die  Anwendungsweise 
des  Antifebrins.    Deutsche  Med.-Ztg.,  Berlin,  1890,  11 :  865,  875. 

(1)  Young  woman:  Two  doses  of  15  grains  of  acetanilid  with  a  half 
hour  interval  were  followed  by  cyanosis.  (2)  Following  the  ingestion  of 
2  doses  of  15  grains  of  acetanilid  the  patient  felt  very  weak  and  was  prone 
to  fall  asleep  whether  walking  or  standing.  (3)  Ingestion  of  1  drachm  of 
acetanilid  with  suicidal  intent  was  followed  by  great  w^eakness,  cyanosis, 
and  persistent  vomiting.  (4)  Girl,  22,  acute  rheumatism:  The  ingestion 
of  7.5  grains  of  acetanilid  3  times  daily  until  5  doses  had  been  taken  was 
followed  by  the  appearance  of  an  urticarial  eruption. 

MoLLOFF.     Discussion  of  paper  by   Khakanoff,  1889.     Trans.   Med.    Surg.   Re- 
porter, Philadelphia,  1890,   62:  83. 

In  two  cases  collapse  followed  the  ingestion  of  one  7-grain  dose  of 
acetanilid. 

Morehouse,  O.  E.    Antifebrin  rash.     Montreal  Med.  J.,  1890-91,  19:  46. 

(1)  Man,  45,  pneumonia:  Was  given  8  grains  of  acetanilid,  and  four 
hours  later  8  grains  more.  An  erythematous  rash  appeared  upon  the  entire 
body,  lasting  six  days.  (2)  Girl,  19,  typhoid:  Six  grains  of  acetanilid 
caused  the  appearance  of  a  rash  resembling  urticaria  on  face  and  chest. 
Four  hours  later  5  grains  more  caused  the  rash  to  spread  to  the  arms. 
Temperature  fell,  accompanied  by  sweating.  Rash  disappeared  after  five 
days. 

Preiningeb,  v.     Otrava  antifebrinem.     Casopis  lekafu  v  ceskych,  1890,  29 :  225. 
Abs.,  Sajous,  1891,  5:  A-2. 

Report  of  a  case  of  poisoning  in  which  acetanilid  appears  to  have  had  a 
cumulative  effect. 

Scott,  J.  T.    Some  peculiar  results  following  the  use  of  acetanilide  in  typhoid 
fever;  report  of  three  cases.     Cincinnati  Lancet-Clinic,  1890  (n.  s.),  24:  65. 

(1)  Child,  3  or  4  years  old,  typhoid:  Six  grains  of  acetanilid  3  times  a 
day  caused  chills  and  cyanosis  of  the  entire  skin,  lasting  from  one-half 
hour  to  one  and  one-half  hours  after  each  dose.  Subsequently  3  grains 
caused  a  chill,  and  the  administration  of  the  drug  was  discontinued. 
(2)  Youth,  24,  typhoid:  Acetanilid,  6  grains  3  times  daily,  caused  on  2 
occasions  severe  chills  and  profuse  sweating.  Drug  discontinued.  (3)  Ty- 
phoid patient  was  given  from  18  to  24  grains  of  acetanilid  daily.  Chills 
appeared  and  increased  in  number  and  se^'e^ity  until  the  patient  was 
having  4  or  5  a  day.    Acetanilid  was  discontinued  and  the  rigors  ceased. 


LITERATURE   ON   ACETANILID   POISONING.  35 

SuTTLE,  I,  N.     Case  of  autifebriu   habit.     New  Orleans,   Med.  and   Sure    J. 
1889-90  (n.  s.),  17   (2):  896. 

The  case  is  reported  to  illustrate  the  insidious  onset  of  the  acetanilid 
habit  and  its  pernicious  effect  on  the  blood.  Man,  with  necrosis  of  the 
tibia,  took  acetanilid  in  large  doses  for  pain.  He  became  addicted  to  its 
use,  and  is  said  to  have  taken  as  much  as  a  teaspoouful  at  a  time.  The 
evil  effect  on  the  blood  was  shown  by  the  excessive  pallor  of  the  skin. 

Taylor.  W.  H.     Report  of  toxic  effect  of  acetanilid.     Cincinnati  Lancet-Clinic, 
1890  (n.  s.),  24:  683. 

(1)  Woman,  26,  advanced  in  pregnancy,  urine  contained  albumin:  At 
5  p.  m.  and  7  p.  m.  she  took  5-grain  doses  of  acetanilid.  At  10  p.  m.  her 
physician  found  her  greatly  prostrated  with  deep  cyanosis,  pinched  features, 
subnormal  temperature,  cool  moist  skin,  and  headache.  Her  temperature 
remained  subnormal  for  ten  days.  (2)  Woman,  19,  six  mouths  pregnant: 
Was  given  10  grains  of  acetanilid  for  fever.  Her  temperature  fell  rapidly 
to  95°,  pulse  ran  up  to  120,  and  skin  became  moist  and  cool.  There  was 
slight  cyanosis  and  some  prostration. 

Thomas,  W.  H.     Acetanilid.     Report  of  a  fatal  case.     Indiana  Med.  J.,  Indian- 
apolis, 1890,  9:  67. 

(1)  Author  expresses  the  opinion  that  5  grains  of  acetanilid  caused  the 
death  of  a  woman  suffering  from  neuralgia  of  the  head  and  stomach.  May 
1,  at  4  p.  m.,  the  patient's  temperature  was  104  and  her  pulse  120,  full  and 
strong.  She  was  sponged  and  given  5  grains  of  acetanilid.  Her  tempera- 
ture fell  rapidly,  accompanied  by  symptoms  of  collapse,  and  she  died  nine 
hours  after  taking  the  dose.  No  record  of  autopsy.  (2)  Ingestion  of  10 
grains  of  acetanilid  was  followed  by  symptoms  of  collapse. 

ViEBHUFF.  J.     I]in  Fall  von  Antifebrinvergiftung.     St.  Petersb.  med.  Wochenschr., 
1S90  (N.  F.),  7:  1.39. 

Woman  took  two  teaspoonfuls  of  acetanilid  on  an  empty  stomach.  She 
vomited  after  drinking  milk  and  then  a  solution  of  alum,  but  cyanosis 
appeared,  and  she  went  into  a  state  of  collapse  which  lasted  three  hours. 

Wolff,   J.      Ein    Fall    von   Antifebrinvergiftung.     Deutsche    Med.-Ztg.,    Berlin, 
1890,  11:  .53.5. 

Woman,  40:  Took  7.5  drachms  of  acetanilid  with  suicidal  intent.  This 
was  followed  by  collapse  and  coma,  and  in  addition  hematuria. 

1Q91. 

P.ROXNER,  H.     (,'ase  of  pus  in  the  pericardium  treated  bv  incision  and  drainage. 
Brit.  Med.  J.,  London,  1891,  1 :  350. 

Girl,  11:  A  single  dose  of  7.5  grains  of  acetanilid  caused  a  raiiid  fall  in 
temperature  and  symptoms  of  collapse. 

"   \KK.  .1.  R.     Clinical  observations  of  acetanilide.     Med.  Surg.  Reportci-,  I'liila 
delphia,  1891,  65:  729. 

Girl,  14:  A  4-grain  dose  of  acetanilid  caused  cyanosis  and  collapse. 

DuNAOAN,    T.    M.      Subnormal    tcmixTature    from    aniifchrin.      Memphis    Med. 
Month.,  1891,  11  :  123. 

.Man,  10:  The  ingestion  of  11  grains  of  acetanilid  in  2  doses  cau.sed 
cyanosis  and  subnormal   fenijierature. 


36  ACETANILID,    ANTIPYEIN,    AND   PHENACETIN. 

Easley,  E.  p.  Fatffl  case  of  acetauilide  poisoning.  (Letter  to  editor.)  Amer. 
Pi-act.  and  News,  Louisville,  1891,  12 :  178. 

Woman,  22,  took  by  mistake  24  grains  of  antikamnia,  supposed  to  repre- 
sent 18  grains  of  acetanilid.  In  a  few  minutes  she  was  wildly  delirious. 
She  then  became  unconscious.  Death  occurred  about  ten  hours  after 
ingestion  of  the  drug.  There  was  deep  cyanosis  of  the  entire  body. 
Autopsy  failed  to  show  any  lesion  as  a  cause  for  death. 

Haee,  H.  a.  Fever:  Its  pathology  and  treatment  by  antipyretics.  Phila- 
delphia and  London,  1891,  p.  89. 

A  dose  of  5  grains  of  acetanilid  caused  collapse  in  a  case  of  typhoid 
fever. 

Hawkins-Ambler,  G.  A.  Antifebrin  in  typhoid  fever.  Brit.  Med.  J.,  London, 
1891,  1:  172. 

(1)  Woman,  49,  typhoid:  Four  grains  of  acetanilid  caused  collapse. 
(2)  Woman,  35,  typhoid:  A  dose  of  4  grains  of  acetanilid  caused  marked 
prostration. 

HoRTON,  F.  Prolonged  subnormal  temperature  following  the  administration  of 
antifebrin.     Med.  News,  Philadelphia,  1891,  59:  712. 

A  typhoid  fever  patient  was  given  4  grains  of  acetanilid  and  three- 
fourths  of  a  grain  of  camphor  at  10  a.  m.,  and  the  same  dose  at  3  p.  m. 
At  6  p.  m.  the  temperature,  which  had  been  104°,  was  97°.  It  ran  between 
this  and  94.6°  for  forty-eight  hours,  when  it  rose  rapidly  to  104°. 

Spencer.     Poisoning  by  antifebrin.     Canad.  Pract.,  Toronto,  1891,  16:  163. 

Child,  5,  whooping  cough :  Ingestion  of  a  drachm  of  acetanilid  taken  by 
mistake  caused  deep  cyanosis  and  slowed  respiration. 

1892. 

Grier,  W.  F.  The  toxic  effects  of  antifebrin  complicated  with  alcoholism. 
Med.  Rec,  New  York,  1892,  42:  511. 

Woman,  45 :  Ingestion  of  40  grains  of  acetanilid  within  eleven  hours 
caused  marked  cyanosis,  increasing  rapidity  of  the  pulse,  swelling  of  the 
tongue,  and  great  restlessness. 

J.  W.  C.     Case  of  acetanilide  poisoning.    Med.  Rev.,  St.  Louis,  1892,  25 :  412. 

Woman,  36,  influenza  :  Took  about  40  grains  of  acetanilid  in  divided  doses 
within  four  hours.  There  followed  cyanosis  of  the  face  and  lips,  semi- 
consciousness, delirium,  and  symptoms  of  collapse. 

Kroneeld,  a.  Ueber  Antifebrinvergiftung.  Wien.  med.  Wochenschr.,  1892, 
42:  1457. 

Man,  24 :  Took  3  drachms  of  acetanilid  with  suicidal  intent.  Within 
thirty  minutes  this  was  followed  by  dizziness,  nausea,  pain  in  the  region  of 
the  stomach,  unconsciousness,  and  slight  cyanosis. 

Wakfvinge,  F.  W.  Redogorelse  for  de  forgiftningsfall  som  forekommit  h 
Sabbatsbergs  sjukhus  under  aren  1879-91.  Antifebrin.  Hygiea  Stock- 
holm, 1892,  54   (1)  :  238. 

Reports  two  cases  of  poisoning  by  acetanilid.     Both  patients  recovered. 


LITERATURE   ON   ACETANILID   POISONING.  37 

1S93. 

Bell.  G.     Vier  Falle  von  Antifebrinvergiftimg.    Memorabilieu,  Heilbroun.  1S93, 
38  (N.  F.  13)  :  535. 

(1)  Man,  past  70:  Ingestion  of  a  heaping  teaspoonfnl  of  acetanilid  was 
followed  by  cyanosis  and  symptoms  of  depression.  (2  and  3)  Each  patient 
took  one-half  teasijoonful  of  acetanilid.  One  complained  of  dizziness,  weak- 
ness, shortness  of  breath,  and  cyanosis  of  the  finger  nails,  and  the  other 
slept  for  two  houi-s.  (4)  "Woman,  75:  Ingestion  of  an  ounce  of  acetanilid 
in  five  days,  in  teaspoonfnl  doses,  was  followed  by  weakness,  drowsiness, 
and  dyspnea. 

KoKAWA.  B.     Antifebrin  jutokusei   Shiken    (antifebrin  poisoning).     Tokujima 
Igakkwai  Zashi.,  1S93,  No.  13,  p.  8. 

1894. 

Davis.  .7.  S.     A  report  of  three  cases  of  addiction  to  the  coal-tar  derivatives. 
Amer.  Med.-Snrg.  Bui.,  1894,  7:  1490. 

(1)  Man,  63:  Chronic  bronchitis  and  cardiac  palpitation  for  two  years. 
Pulse  160  and  weak,  becoming  irregular  upon  exertion.  Anorexia,  consti- 
pation, cyanosis,  varying  in  degree  at  different  times.  Had  been  addicted 
to  the  use  of  acetanilid  for  a  year,  taking  40  to  60  grains  daily.  Last  two 
months  he  had  been  running  down  until  he  was  confined  to  bed.  Dose  of 
acetanilid  was  reduced  to  10  grains  daily.  He  gradually  improved  and  at 
end  of  a  year  was  in  fairly  good  health.  (2)  Man,  32:  Suffered  from 
cyanosis,  coldness  of  extremities,  insomnia,  anorexia,  constipation,  nervous- 
ness, and  anemia.  I'rine:  Specific  gravity  1.012,  albuminous.  Heart,  rapid 
and  feeble.  Had  been  taking  acetanilid  for  eight  months,  12  to  40  grains 
daily,  and  his  health  had  failed  rapidly.  The  drug  was  entirely  withdrawn 
and  after  a  month  he  was  in  fairly  good  condition.  After  abstaining  for 
eight  months  he  again  contracted  the  habit  and  his  health  again  became 
impaired. 

HiLBEKT,  R.     Hochgradige  Amblyopic  nach  Gebrauch  von  Acetanilid.     Memora- 
bilieu, Heilbroun,  1894  (N.  P.),  14:  65. 

Ingestion  of  three  15-grain  doses  of  acetanilid  at  short  intervals  caused 
vertigo  and  dimness  of  visiou.  After  twenty-ifour  hours  the  sight  was 
again  normal. 

Lynbomndkoff.  p.  F.     Sluchai  otravleniya  antifebrinom  (Antifebrin  poisoning). 
Voyenno-Med.  J.,  St.  Petersburg,  1894,  181   (unofficial  pt.,  sec.  2)  :  29. 

Morton,  T.   S.  K.     Acetanilid  as  an  antiseptic.     Proc.  of  the  Phila.  Co.  Med. 
See,  1894,  15:  469. 

(1)  Infant,  14  months:  Large  wound  in  hip,  packed  willi  10  jicr  cent 
acetanilid  g.iuze.  In  four  hours  the  temperature  dropped  5°.  with  symi)- 
tonis  of  marked  depression.  (2)  .Man,  57:  Extensive  sii])erficial  scald. 
Two  drachms  of  acetanilid  dusted  over  the  surface  caused  cyanosis,  ex- 
ceHslve  yawning,  delirium,  and  synii>tonis  of  depression. 

\\'(>tn>s,  (i.  W.     The  use  of  ncelaiiilid  in  medicine  and  surgery.     J.  Amer.  .Med. 
A8SOC.,  Chicago,  1894,  23:  KKJ. 

The  a[>[)!icali<jn  of  acefanllid  powder  to  an  ulcerated  surface  was  folloAved 
by  dee|)  ryanosls  of  the  nose,  lii)S,  and  ti|)S  of  the  fingers  and  toes. 


38  ACETANILID,    AISTTIPYEIN,    AND    PHENACETIN. 

1895. 

Briggs,  W.  a.     Poisoning  from  the  local  application  of  acetanilid.     Occidental 
Med.  T:'imes.     Sacramento,  1895,  9:  596. 

The  use  of  acetanilid  as  a  dressing  for  circumcision  in  an  infant  1  week 
old  was  followed  by  deep  cyanosis,  pinched  expression,  and  cold  extremities. 

Broberg,  J.  A.     Toxic  effects  from  acetanilid  applied  topically.     Med.   News, 
Philadelphia,  1895,  67:  664. 

The  application  of  acetanilid  to  the  skin  of  the  groins  for  irritation 
caused  cyanosis, 

Carmalt,  W.  H.    Toxic  effects  from  acetanilid  applied  topically.    Yale  Med.  J., 
New  Haven,  1895-96,  2:  131. 

Girl,  18 :  Acetanilid,  applied  to  an  ulcer  every  four  hours  for  twenty-four 
hours,  caused  cyanosis. 

Hubbard,  S.  D.     A  case  of  poisoning  due  to  antikamnia.     Codex  Med.  Phila- 
delphia, 1895-96,  2:  198. 

Woman,  40 :  Ingestion  of  five  powders  containing  antikamnia,  15  grains 
each,  was  followed  by  pallor  of  face,  cyanosis  of  the  nose,  ears,  eyelids, 
and  extremities,  unconsciousness,  and  symptoms  of  collapse. 

RosENBERGER,  R.  C.     A  caso  of  acetanllid  poisoning;   recovery.     Philadelphia 
Polyclinic,  1895,  4:  460. 

Infant,  16  days  old  :  Hemorrhage  from  umbilicus.  Application  of  a  pow- 
der of  equal  parts  of  acetanilid  and  boric  acid  twice  daily  for  three  days 
caused  marked  cyanosis  of  face,  lips,  fingers,  and  toes,  cold  extremities,  and 
labored  breathing. 

Sauter,   C.     Cyanotic  symptoms  after  local  application  of  acetanilid.     Loiiis- 
ville  Med.  Month.,  1895-96,  2:  341. 

Child,  3  years,  eczema  of  neck :  A  powder  consisting  of  1  part  acetanilid 
and  3  parts  bismuth  subnitrate  was  applied  3  times  daily.  Second  appli- 
cation of  a  new  supply  caused  deep  cyanosis,  with  labored  breathing  and 
other  evidences  of  distress.     Symptoms  followed  every  application  of  the 

powder. 

1S96. 

Acetanilid  poisoning.     Med.  Brief,  1896,  24:  86. 

Man :  Ingestion  of  eight  doses  of  acetanilid,  15  grains  each,  within  six 
hours,  caused  deep  cyanosis. 

BiGELOw,  B.     Acetanilid  poisoning.     Med.  Brief,  1896,  24 :  703. 

Ingestion  of  acetanilid  by  two  patients,  both  women,  caused  deep  cya- 
nosis, black  discoloration  of  the  lips,  tongue,  intense  dyspnea,  and  complete 
prostration. 

Brindley,  a.  E.     Antifebrin  poisoning.     Brit.  Med.  J.,  London,  1896,  2:  653. 

Woman,  33 :  Admitted  to  hospital  for  spinal  disorder.  Skin  and  mucous 
membranes  cyanotic.  Had  been  taking  kaputine  powders  secretly  for  a 
year.  The  powders  were  found  to  consist  mainly  of  acetanilid.  Upon 
withdrawal  the  cyanosis  disappeared. 

Brodnax,  B.  H.     Poisoning  by  acetanilid  and  bismuth.     J.  Amer,  Med.  Assoc, 
Chicago,  1896,  26:  788.  ' 

Six  cases  of  cyanosis  in  children  under  18  months  of  age  following  the 
administration  of  acetanilid. 


LITERATURE    ON    ACETANILID    POISONING.  39 

BuxcE,  W.  C.     Acetanilid  poisoninir.     Ooluuibns  Med.  J.,  1896,  17:  505. 

Man  :  Ingestion  of  a  heaping  tablespoonfnl  of  acetanilid  caused  vertigo, 
deep  cyanosis,  unconsciousness,  rigidity  of  the  body,  and  collapse. 

Editorial.     Poisoning  by  antifebrin.     Brit.  Med.  J.,  London,  1896,  2:  89. 

Refers  to  the  death  of  a  young  woman  from  taking  "  daisy  powders  "  for 
headache.  The  powders  were  found  to  contain  from  3  to  10  grains  each  of 
acetanilid. 

Newton,  R.  C.     A  case  of  poisoning  from  the  external  use  of  acetanilid.     Med. 
Rec.,  New  York.  1896,  49:  333. 

Girl.  4  :  Application  of  acetanilid  to  an  ulcer  on  the  hand  on  two  occasions 
caused  vomiting,  cyanosis,  and  collapse. 

Ringer,  S.     Case  of  antifebrin  poisoning.     Brit.  Med.  J.,  Loudon,  1S96,  2:  195. 
Woman,  28:  Habitual  use  of  acetanilid  in  the  foi'm  of  Ellis's  daisy  head- 
ache powders  caused  cyanosis  and  headache  which  required  hospital  treat- 
ment. 

Rook.   ('.  W.     Poisoning  by  acetanilid.     J.  Amer,  Med.  Assoc,  Chicago,  1896, 
26:  239. 

(1)  Baby,  4  days  old:  Powder  consisting  of  equal  parts  of  acetanilid  and 
bismuth  was  applied  in  the  afternoon  and  evening  to  an  inflamed  area  of 
the  skin.  Next  morning  the  body  was  deeply  cyanosed,  and  the  child  died 
a  few  hours  later.  (2)  Application  of  a  similar  powder  in  case  of  an 
infant  2  days  old  caused  intense  cyanosis. 

Speed,  J.  M.     Acetanilid  poisoning.     Med.  Brief,  1896,  24:  837. 

Child,  1  year  old:  Application  of  a  powder  consisting  of  equal  parts  of 
acetanilid  and  boracic  acid  to  an  ulcer  caused  deep  cyanosis  and  depres- 
sion and  energetic  treatment  was  required  to  save  the  child's  life. 

VoiTSEKiiovsKi,  N.  F.     (A  case  of  poisoning  by  antifebrin.)     Voyenno-med.  J., 
St.  Petersburg.  18f)6,  185    (2  Sec.)  :  16. 

Was,  L.     Overdose  of  acetanilid.     Med.  Brief,  1896,  24:  854. 

Three  cases  of  poisoning  by  acetanilid  characterized  by  slow,  weak,  and 
irregular  pulse. 

1897. 

Boi-AND,  E.  S.     A  caution  against  the  use  of  antif('i)rin  on  extensively  blistered 
surfaces.     Boston  .Med.  and  Surg.  J.,  1897,  137:  95. 

Voutli,  19:  Application  of  acetanilid  to  a  burned  area  on  the  back  was 
f<»llowe<l  by  general  cyanosis  and  collapse. 

<;\KTMAN,  L.  N.,  and  Bai.i-,  M.   V.     A  case  of  acetanilid  poisoning.     I'hiladel- 
phia  Polyclinic,  1S97,  «:  38L 

Child,  3J  years:  A  scalded  surface  was  dressed  with  3  ounces  of 
10  per  <-ent  ointment  of  aeehinilld.  Two  days  later  3  ounces  were  again 
applied  and  the  child  began  to  turn  blue.  Cyanosis  deepened  until  the 
Kkin  and  niucoits  membranes  became  blackish-blue,  and  sym|)t(jms  of  col- 
lapse followed. 


40  ACETAlSriLTD,    ANTIPYEIN,    AND    PHENACETIN. 

Slifee,  G.  B.    A  case  of  acetauilid  poisoning.    Therap.  Gaz.,  Detroit  and  Phila- 
delphia, 1897,    (3),  13:  360. 

Woman,  21 :  Took  a  little  acetanilid  on  the  end  of  a  spoon  twice,  and 
then  a  teaspoonful.  This  was  followed  by  vertigo,  faintness,  cyanosis,  semi- 
consciousness, and  symptoms  of  collapse.  There  was  suppression  of  urine 
until  noon  of  the  following  day. 

Snow,  I.  M.     Acetanilid  poisoning  in  a  newly  born  infant :  Absorption  from  the 
umbilicus.     Med.  and  Surg.  Reporter,  Philadelphia,  1897,  76:  794. 

Application  of  about  a  drachm  of  acetanilid  to  the  umbilicus  of  an  infant 
7  days  old  caused  deep  cyanosis  and  symptoms  of  collapse.  The  child  lost 
1  pound  in  three  days, 

1S98. 

Ballou,  p.  V.     Unusual  symptoms  following  the  administration  of  antifebrin. 
Med.  News,  New  York,  1898,  72:  791. 

Man,  45 :  Ingestion  of  10  grains  of  acetanilid  was  followed  by  the  ap- 
pearance of  a  general  eruption,  resembling  that  of  scarlatina,  with  intense 
itching,  irregularity  of  the  pulse,  and  a  sense  of  impending  danger. 

Bkown,  p.  K.     a  fatal  case  of  acetanilid  poisoning.     Pacific  Rec.   Med,   and 
Surg.,  San  Francisco,  1898-99,  13:  197. 

Man,  37 :  Brought  to  hospital  thirty-six  hours  after  he  had  taken  50 
grains  of  acetanilid  within  a  few  hours.  Was  kept  alive  nine  days.  Fre- 
quent vomiting,  general  hyperesthesia,  deep  cyanosis  of  lips,  gums,  and 
extremities,  increased  reflexes,  lowered  blood  pressure,  the  pulse  rate 
steadily  rising  until  just  before  the  end.  All  the  symptoms  of  collapse. 
Progressive  destruction  of  red  corpuscles  to  1,116,000,  with  30  per  cent  of 
hemoglobin  on  day  of  death,  Leucocytosis.  Alkalinity  of  the  blood  re- 
duced SO  per  cent.  Hemoglobinuria  began  twenty-four  hours  after  inges- 
tion. Suppression  of  urine  three  days  before  death.  Acute  diffuse 
nephritis.     Hemorrhage  from  intestines.     Acute  progressive  jaundice. 

Buehler,  G.  V.     Case  of  acetanilid  poisoning.     Atlantic  Med.  Weekly,  Prov- 
idence, 1898,  9:  276. 

Man,  21,  burn  of  entire  back:  Application  of  not  more  than  1  to  1.5 
drachms  of  acetanilid  was  followed  by  cyanosis,  unconsciousness,  and 
collapse. 

1899. 

GiLMORE,  A.  W,     Acetanilid  habit.     Philadelphia  Med.  J.,  1899,  3:  1423. 

Woman,  58 :  For  pain  and  insomnia  took  acetanilid  regularly  for  twenty 
months.  At  first  she  took  2.5  grains  at  a  dose,  but  gradually  increased  it 
to  10. 

Wescott,  T.  S.    a  case  of  acetanilid  poisoning  from  external  absorption  in  an 
infant.     Pediatrics,  New  York,  1899,  7:  539. 

Application  of  a  dusting  powder  consisting  of  acetanilid  in  the  folds 
of  the  groin  and  thighs  for  chafing,  caused  deep  cyanosis. 

1900. 

(Jaines,  G.  W.    a  case  of  acetanilid  habit.     New  Orleans  Med,  and  Surg    J 
1900-1901,  53:  30. 

Adult  negro:  Had  been  taking  acetanilid  for  rheumatic  pain  for  four 
years,  and  recently  had  been  taking  as  much  as  2  ounces  each  week. 


LITERATURE   ON   ACETANILID   POISONING.  41 

Summers.  O.  R.    Acetanilid  idiosyncrasy.     Indiana  Med.  J.,  Indianapolis,  1899- 
1900.  18:  382. 

Woman.  26:  Ingestion  of  8  grains  of  acetanilid  in  2  doses  with  an  interval 
of  one-half  hour  caused  nausea,  vertigo,  dyspnea,  deep  cyanosis  of  lips  and 
finger  tips,  and  all  the  symptoms  of  collapse.  There  were  also  periods  of 
convulsive  movements  with  partial  loss  of  consciousness. 

1901. 

Eaep.   S.  E.     a  case  resembling  morbus  cseruleus  probably  due  to  a  dusting 
powder  containing  acetanilid.     Pediatrics,  New  York,  1901,  12:  93. 

Child,  one  month  old :  Thought  at  first  to  have  morbus  cseruleus.  Cyano- 
sis of  skin  and  mucous  membranes.  Lips  and  tongue  almost  black.  Cold, 
clammy  skin,  mental  dullness,  slowed  respiration.  Later  it  was  ascertained 
that  a  raw  area  of  skin  had  been  dusted  for  several  days  with  a  powder 
consisting  of  equal  parts  of  acetanilid  and  boric  acid. 

Manasses.  J.  L.    Two  cases  of  acetanilid  poisoning  in  children  from  absorption 
from  external  wounds.     Internat.  Med.  Mag.,  New  York,  1901,  10:  278. 

(1)  Child.  6  weeks  old:  Frequent  application  of  a  powder  consisting  of 
equal  parts  of  acetanilid  and  subgallate  of  bismuth  to  an  infiamed  area  on 
the  buttocks  was  followed  by  deep  cyanosis  of  the  entire  skin.  (2)  Boy,  2i 
years :  Similar  powder  dusted  on  a  scalded  surface  caused  cyanosis  of 
lips,  ears,  and  finger  tips,  extending  to  the  entire  skin,  and  symptoms  of 
depression. 

Stewart,  F.  T.    Toxic  effects  of  acetanilid.    Philadelphia  Med.  J.,  1901,  8 :  379. 

(1)  A  denuded  surface,  made  by  taking  skin  grafts,  was  copiously  dusted 
with  acetanilid.  Next  morning  the  patient  was  cyanotic,  collapsed,  and 
uuconscious.  (2)  Child,  4  months:  Application  of  a  powder  consisting  of 
one-half  drachm  of  calomel  and  two  drachms  each  of  bismuth  subgallate 
and  acetanilid  to  the  skin  was  followed  by  intense  cyanosis. 

Teacy,  E.  a.    Acetanilid  poisoning.    Pediatrics,  New  York,  1901,  12:  385. 

Baby,  few  days  old  :  Application  of  a  powder  consisting  of  equal  parts  of 
acetanilid  and  stearate  of  zinc  to  a  raw  area  on  the  buttocks  several  times 
in  twenty-four  hours  was  followed  by  intense  cyanosis. 

1903. 

Cabot,   R.  C.     Methemoglohineiiiiu  due  to  acetanilid  but  without  any  marked 
constitutional  symptoms.     Philadelphia  Med.  J.,  1902,  10:  848. 

Man,  .35,  entered  hospital  in  .July  in  a  condition  of  intense  cyanosis. 
Six  months  before  he  had  begun  to  take  acetanilid  for  pain,  and  had  con- 
tinued to  take  about  six  5-grain  powders  daily.  Blood  drop,  chocolate 
colored;   urine  brownish-red  and  gave  spectrum  of  metheuioglobln, 

Ki-EiNPFn-ER,    E.    A.     Acetanilid   cyanosis.      New    Orleans   Med.    and    Surg.    J., 
1902-3,  65:  166. 

Adult,  male;  Five  grains  of  acc(;uiilid  adniiiiistered  every  four  hours 
for  three  days  <ause<l  marked  cyanosis  of  lips,  gums,  and  mouth,  and 
marked  prostratioQ. 


42  ACETANILID,   ANTIPYRIN,   AND  PHENACETIN. 

1903. 
Hall    J   N.,  and  McGraw,  H.  R.     Chronic  cyanosis  from  acetanilid  poisoning. 
Boston  Med.  and  Surg.  J.,  1903,  149 :  626. 

Man,  50 :  Habitual  use  of  acetanilid,  30  to  40  grains  daily,  for  six  months 
caused  a  loss  of  20  pounds  in  weight,  cyanosis  of  face  and  mucous  mem- 
branes, deterioration  in  the  quality  of  the  blood,  and  marked  general 
weakness. 

Luce,  T.  W.  The  acetanilid  habit— Report  of  two  cases.  Amer.  Med.,  Phila- 
delphia, 1903,  6:  502. 

Two  cases  in  which  the  habitual  use  of  acetanilid  by  women  caused 
cyanosis,  ehiaciation,  general  debility,  and  invalidism.  In  the  case  of  one  of 
the  patients  there  were  convulsive  seizures. 

Stengel,  A.,  and  White,  C.  Y.  A  report  of  a  case  of  chronic  acetanilid  poison- 
ing, with  marked  alterations  in  the  blood.  Univ.  Penn.  Med.  Bui.,  1902-3, 
15:  462. 

Woman,  25:  Habitual  use  of  acetanilid  for  about  seven  years  caused 
cyanosis  varying  in  degree  according  to  the  amount  taken,  deterioration 
in  the  quality  of  the  blood,  and  general  debility  amounting  to  invalidism. 

1904. 

Elmquist,  a.  G.  J.  En  stor  Dosis  Antifebrin.  Hosp.-Tid.  Kjobenhavn,  1904, 
4.  R.,  12:  350. 

Recovery  followed  the  ingestion  of  120  grains  of  acetanilid  taken  by  a 
woman   with  suicidal   intent. 

1905- 

MiLLEE,  J.  L.  Poisoning  by  orangeine.  J.  Amer.  Med.  Assoc,  Chicago,  1905, 
44:  1989. 

A  young  woman,  physically  sound,  had  been  taking  orangeine  powders  for 
several  weeks  for  insomnia.  Her  family  noticed  that  she  was  cyanotic  and 
sent  for  a  physician,  who  found  deep  cyanosis  of  face,  lips,  and  extremities. 
She  was  also  faint  and  chilly.  Had  taken  6  of  the  powders  within  eight 
hours.  Her  family  promised  that  she  should  obtain  no  more,  but  three 
days  afterwards  she  was  found  dead  in  bed  in  the  morning.  Coroner's 
verdict:  "  Death  was  from  the  effect  of  an  overdose  of  orangeine  powders 
administered  by  her  own  hand,  whether  accidentally  or  otherwise  un- 
known to  the  jury." 

Peobasco,  E.  B.  Acetanilid  poisoning.  New  York  State  J.  Med.,  1905,  5:  318. 
(1)  Man,  25,  suffering  from  an  attack  of  typhoid:  Five-grain  doses  of 
acetanilid  every  three  or  four  hours  caused  cyanosis  and  prostration. 
(2)  Girl,  13,  influenza  :  Acetanilid  in  5-grain  doses  every  three  or  four 
hours  caused  cyanosis  and  prostration.  (3)  Woman,  30:  Ingestion  of 
antikamnia  tablets  caused  cyanosis  and  collapse.  (4)  Man,  33:  Ingestion 
of  10  migraine  tablets,  each  containing  2.5  grains  of  acetanilid,  between 
10  a.  m.  and  2  p.  m.,  was  followed  by  deep  cyanosis  and  collapse. 

Stengel,  A.  Chronic  acetanilid  poisoning;  report  of  two  additional  cases. 
J.  Amer.  Med.  Assoc,  Chicago,  1905,  45 :  243. 

(1)  Man,  38:  Habitual  use  of  acetanilid  in  the  form  of  cephalgin  for 
a  year  caused  progressive  loss  of  flesh  and  strength,  somnolence,  cyanosis, 
increasing  weakness,  irritability  of  temper,  and  irregular  heart  action,  the 
pulse  becoming  rapid  on  slight  exertion.  (2)  Woman,  27:  Habitual  use  of 
about  20  grains  of  acetanilid  daily  in  the  form  of  headache  tablets  caused 
progressive  loss  of  health  and  strength,  with  cj^anosis,  dyspnea,  headache, 
palpitation  of  the  heart,  increasing  rapidity  of  the  pulse  and  respiration 
especially  on  exertion,  and  deterioration  in  the  quality  of  the  blood. 


LITERATURE   ON   ACETANILID   POISONING.  43 

STEWA3T,  D.  D.     Chronic  poisouiug  by  acetauilid.    J.  Amer.  Med.  Assoc,  Chi- 
cago, 1905,  44:  1725. 

(1)  Man,  40:  Habitual  use  of  acetauilid  for  two  years  caused  gradual 
loss  of  health,  cyanosis,  general  debility  with  loss  of  cardiac  tone,  and 
deterioration  in  the  quality  of  the  blood.  (2)  Man,  50:  Habitual  use  of 
acetauilid  for  two  years  caused  progressive  loss  of  flesh  and  strength, 
the  weight  falling  from  110  to  116,  frequent  vomiting,  cyanosis,  deteriora- 
tion in  the  quality  of  the  blood,  mental  dullness,  and  general  debility 
amounting  to  invalidism. 

1906. 

AusTiiv,  A.  E.,  and  Larrabee,  R.  C.     Acetauilid  poisoning  from  the  use  of  pro- 
prietary headache  powders.     J.  Amer.  Med.  Assoc,  Chicago,  1906,  46:  1680. 

Woman,  43:  Habitual  use  of  nervease  powders  (about  5  grains  of  acet- 
auilid each),  often  6  to  10  daily,  caused  intense  cyanosis  and  deterioration 
in  the  quality  of  the  blood.  (2)  Woman:  Habitual  use  of  6  nervease 
powders  daily  caused  nausea,  general  debility,  cyanosis,  and  deterioration 
in  the  quality  of  the  blood. 

Bergman,  N.     Remarks  on  acetauilid.     Clinique,  Chicago,  1906,  27:  271. 

(1)  Administration  of  two  5-grain  doses  of  acetauilid  with  an  interval  of 
one  hour  to  a  baby  2  weeks  old  was  followed  by  coma,  cj^anosis,  and  col- 
lapse. (2)  Two  hundred  grains  of  acetauilid  taken  within  twenty-four 
hours  caused  cyanosis,  profound  coma,  and  death. 

Blackburn,  A.  K.       Acetauilid  poisoning  from  bromo-seltzer.       J.  Amer.  Med. 
Assoc,  Chicago,  1906,  4(>:  1767. 

Man,  22 :  Habitual  use  of  bromo-seltzer  over  a  period  of  six  months 
caused  mental  dullness  and  depression,  general  weakness  and  indisposition 
to  exertion,  and  cyanosis.  The  expression  was  vacant,  the  breath  fetid, 
pulse  rapid  on  exertion. 

Cassady,  D.     Acetauilid  poisoning  by  headache  tablets.     J.  Amer.  Med.  Assoc, 
Chicago,  1906,  47:  2012. 

Woman,  45 :  Accustomed  to  taking  "  Steam's  Headache  Cure."  One 
wafer  an  hour  for  three  hours  caused  cyanosis  and  symjitoms  of  collapse. 

(lOEPP,  R.  .M.     A  case  of  acetauilid  poisoning  from  absorption.     J.  Amer.  Med. 
Assoc,  Chicago.  1906,  47:  359. 

Woman,  37:  (1)  For  eleven  months  she  had  dressed  an  ulcer  of  the  leg 
with  acetauilid,  aiul  during  this  time  she  had  run  down  in  health  and  lost 
70  pounds.  Suffered  from  cyan<jsis,  abdominal  ])ain,  general  nervousness, 
dyspnea,  nausea  and  occasional  vomiting,  headache,  and  dizziness.  Urine 
of  a  dark,  amber  tint.  Blood  examination  showed  anemia.  (2)  Habitual 
use  of  an  aniouuL  of  bronio-selt/.er,  eciuivalent  to  about  HO  grains  of  acet- 
auilid daily. 

Hkmknway.  II.  B.     Death  from  i)ioiiio-seltzer :  case  of  acetauilid  poisoning.     J. 
Amer.  .Med.  Assoc,  Chicago,  11M)6.  47:  21.^)8. 

Woman,  31  :  During  the  last  month  she  had  siiffeicd  from  headaches  for 
wliicli  she  took  bromo-seltzer.  On  October  12  she  took  an  unknown  quan- 
tity. X'omited  l)efore  arrival  of  jthysician.  Examination  showed  a  ])oorly 
nonrJHhed  woman,  !)reathlng  regularly  and  deeply.  Eyes  closed,  body  re- 
laxed, lips  and  fingers  blue.  I'lilse  SO,  soft  and  regular.  Area  of  heart 
dullness  slightly  IncreastMl,  right  ventrical  dilated.  I'upils  dijaled.  She 
sank  suddenly  and  died  at  7.45.  Verdict  of  coroner's  Jury:  "Death  from 
acetauilid  jtoisoning  from  taking  bromo-seltzer."  Autopsy  showed  softiMi- 
ing  of  IIh*  kidrnty  fi'om  [larenclivnialoiis  inllanunal  ion.  'i'liis  condition  had 
given  no  syniptfans  during  life. 


44  ACETANILID,   ANTIPYKIN,   AND   PHENACETIN. 

Hebeick,  J.  B.,  and  Irons,  E.  E.  Chronic  acetanilid  poisoning  with  report  of 
a  case  due  to  absorption  of  the  drug  from  an  ulcer  of  the  leg.  J.  Amer. 
Med.  Assoc,  Chicago,  1906,  46:  351. 

Woman,  50:  For  seven  years  had  applied  acetanilid  to  a  large  ulcer  of 
the  leg.  During  this  time  she  suffered  from  general  nervousness,  mental 
depression,  weakness,  dyspnea,  cyanosis,  and  palpitation.  Sudden  with- 
drawal of  the  drug  caused  maniacal  excitement,  proving  addiction.  Liver 
and  spleen  enlarged.  Blood  showed  secondary  anemia.  Urine  dark  and 
gave  test  for  paramidophenol.  Gradual  withdrawal  of  acetanilid.  Re- 
covery. 

Morgan,  W.  G.  Remarkable  dosage.  Amer.  Med.,  Philadelphia,  1906  (N.  S.), 
1:  245. 

The  ingestion  of  47.5  grains  of  acetanilid  three  times  daily  caused 
cyanosis. 

PucKETT,  C.     Acetanilid  poisoning.     Oklahoma  Med.  News-J.,  1906,  14:  208. 

Man,  49 :  Ingestion  of  about  a  teaspoonful  of  acetanilid  in  4  doses  at 
hourly  intervals  was  followed  by  vertigo  and  general  weakness.  Slept  all 
night,  but  the  next  day  he  was  in  bed  with  intense  cyanosis  and  all 
symptoms  bordering  on   collapse. 

Qtjigley,  D.  T.  Acetanilid  in  bromo-seltzer.  J.  Amer.  Med.  Assoc,  Chicago, 
1906,  46:  454. 

Ingestion  of  a  heaping  tablespoonful  of  bromo-seltzer  by  a  man  caused 
cyanosis  and  symptoms  of  collapse. 

Sutherland,  E,  L.  Acetanilid  poisoning.  Med.  Sentinel,  Portland,  Oreg.,  1906, 
14:  466. 

(1)  Woman,  34:  For  six  weeks  she  had  suffered  from  vertigo,  shortness 
of  breath,  anorexia,  nausea,  and  severe  headaches.  Her  physician  found 
her  unconscious,  cyanosed,  and  in  profound  collapse.  Inquiry  showed  that 
she  had  been  taking  bromo-seltzer  for  two  weeks  in  tablespoonful  doses  for 
pain.  (2)  Woman,  32:  Ingestion  of  perfection  headeache  wafers  over  a 
period  of  three  weeks  caused  nausea  and  vertigo,  attacks  of  syncope, 
cyanosis,  loss  of  memory,  and  difficulty  in  concentrating  the  thoughts. 
Pulse,  135,  soft  and  intermittent;  urine  scant,  1.028.  Convalescence  lasted 
two  months.  (3)  Woman,  39:  Habitual  use  of  headache  powders  contain- 
ing 6  grains  of  acetanilid  powder  each,  caused  nausea,  general  nervousness 
and  debility,  cyanosis,  and  rapid  intermittent  pulse.  (4)  Woman,  69: 
Case  similar  to  the  preceding.  (5)  Woman,  36:  Had  been  taking  bromo- 
seltzer  in  tablespoonful  doses  for  headache  for  two  months.  Collapsed  in 
the  street.     Symptoms  resembled  those  in  preceding  case. 

Tybeell,  J.  B.  Acute  acetanilid  poisoning.  J.  Amer.  Med.  Assoc,  Chicago, 
1906,  46:  955. 

Man,  52:  Ingestion  of  one-half  teaspoonful  of  acetanilid  was  followed 
by  intense  cyanosis,  syncope,  and  collapse. 

1907. 

DoBSON,  L.  A  case  of  poisoning  by  antikamnia.  West  London  Med.  J.,  1907, 
12:  226. 

Man,  54:  Took  twelve  5-grain  tablets  of  antikamnia  at  night.  He  was 
found  in  bed  the  next  morning  and  was  at  first  thought  to  be  dead.  There 
was  an  intense  degree  of  cyanosis  and  severe  symptoms  of  collapse. 


LITERATURE    ON    ACETANILID    POISONING.  45 

Glazebbook,  L.  W.  Chronic  acetanilid  poisoning  from  Harper's  "  brain  food." 
J.  Anier.  Med.  Assoc,  Cliieago,  1907.  49 :  167.3. 

Woman,  4.5:  Habitual  usp  of  acetanilid  in  tlie  form  of  Harper's  brain 
food  caused  general  malaise,  drowsiness,  fatigue  on  slight  exertion,  numb- 
ness of  lower  extremities,  impaired  locomotion,  cyanosis  and  puffiness  of  the 
skin,  tremor  and  rapid  pulse. 

LoEWEXTHAL.  P.  Death  from  Koehler's  headache  powders.  J.  Amer.  Med. 
Assoc.  Chicago.  1907,  48:  813. 

Two  powders  caused  the  death  in  an  hour  and  a  half  of  James  Tobias,  New 
York,  who  "  came  to  his  death  by  acetanilid  poisoning  administered  *  *  * 
in  Koehler's  headache  powders  *  *  *  "  Each  powder  is  said  to  have 
been  composed  of  acetanilid  76  per  cent,  caffein  22  per  cent. 

RooKER,  A.  M.  Case  of  poisoning  by  headache  powders  (Shac).  J.  Amer.  Med. 
Assoc,  Chicago,  1907,  49:  1675. 

Woman,  45,  headache :  One  Steam's  headache  wafer  was  followed  in  half 
an  hour  by  dizziness  and  in  an  hour  by  unconsciousness,  cyanosis,  and  pros- 
tration. 

Sanford.  M.  J.,  and  Van  Wagman,  D.  V.  Death  from  Taylor's  antiheadache 
powders.     J.  Amer,  Med.  Assoc,  Chicago,  1907,  48:  1693. 

Boy.  7,  was  given  a  Taylor's  powder  containing  about  4.5  grains  of  acet- 
anilid at  9  a.  m.,  10.1.5,  and  11  o'clock.  He  soon  became  faint,  the  lips  and 
tongue  became  very  blue,  the  face  yellowish,  and  the  eyes  staring  and  pro- 
truding. At  12.15  convulsions  set  in  and  he  died  at  1  o'clock,  before  the 
arrival  of  a  physician. 

Smedley,  a.  L.  Death  from  acetanilid  poisoning.  J.  Amer.  Med.  Assoc,  Chi- 
cago, 1907,  48:  14.33. 

Man,  29,  weight  190:  Took  three  headache  powders  between  9  and  12 
o'clock,  each  containing  acetanilid  2.5  grains,  caffein  citrate  0.5  grain,  and 
sodium  bicarbonate  3  grains.  He  vomited  twice  and  became  very  w'eak  and 
cyanotic,  with  slow  pulse,  slow  shallow  respiration,  and  intense  headache. 
The  cyanosis  deepened,  collapse  supervened,  and  he  died  in  a  convulsion  at 
4  p.  m.  Autopsy  showed  edema  of  lungs,  dilatation  of  heart,  congestion 
(acute  cloudy  swelling)  of  the  kidneys.  Urine  in  bladder  showed  traces  of 
albumin. 

Strickland,  C.  G.  A  case  of  chronic  acetanilid  poisoning.  Pennsylvania  Med. 
J.,  Athens,  1907-8,   11:  31. 

Woman,  26:  For  six  months  had  been  freely  dusting  a  large  leg  ulcer  with 
acetanilid,  using  a  half  pound  weekly.  P^or  three  months  she  suffered  from 
headache,  paljiitation,  nausea  and  vomiting,  dyspnea,  insomnia,  cyanosis, 
and  abdominal  pain.  I.iver  and  sr)leen  were  enlarged,  and  a  cardiac  mur- 
mur was  present.  Blood  was  chocolate  colored  and  showed  marked  dimi- 
nution in  iiunii»er  of  red  cells  to  1,860,000.  Trine  was  almost  black  and 
gave  test  for  paramidophenol.  Withdrawal  of  the  drug  was  followed  by 
recovery. 

Wynn,  F.  B.  A  case  of  acetanilid  poisoning  from  headache  cai)sules  with  ex- 
treme tachycardia  the  dominant  symptom.  J.  Amer.  Med.  A.S8oc,  Chicago, 
1907,  49:  1027. 

W^oman,  44:  Case  in  wlik-h  the  ingestion  of  6  neuralgic  capsules  (acetan- 
ilid and  caffein)  within  a  few  hours  was  followed  by  nausea,  prostration, 
dyspnea,  pre<:ordlal  anguish,  pallor,  and  extreme  rapidity  of  the  pulse. 
Rate  as  determined  by  sphygmograph  was  210. 


46 


ACETANILID,    ANTIPYEIN,    AND    PHENACETIN. 


ANTIPYRIN. 
INTEODUCTOKY   RESUME. 

In  the  following  bibliography  of  poisoning  by  antipyrin  an  attempt 
has  been  made  to  classify  the  cases  according  to  the  pathological 
effect  produced.  Thus,  under  the  heading  "  Cutaneous  Eruptions  " 
there  are  grouped  the  cases  in  which  symptoms  of  the  skin  appear 
from  the  published  reports  to  have  played  the  most  prominent  and 
important  part  in  the  history  of  the  cases.  This  method  has  been 
adopted  because  it  gives  more  information  with  regard  to  clinical 
history  than  the  mere  title  of  the  published  report  would  convey, 
and  because  it  has  been  found  to  be  impracticable  to  publish  a  full 
abstract  of  each  recorded  case  of  poisoning  by  antipyrin.  It  will 
readily  be  seen,  however,  that  nothing  approaching  accuracy  can  be 
secured  in  this  way.  In  some  of  the  cases  no  one  symptom  or  group 
of  symptoms  appears  from  the  published  reports  to  have  stood  out 
very  prominently  in  the  clinical  picture.  What  ajDpears  to  have 
been  the  most  important  feature  of  the  case  is  often  attended  by 
symptoms  in  other  parts  of  the  body  which  are  almost  if  not  equally 
important.  Thus  many  of  the  skin  cases  present  in  addition  to 
the  cutaneous  symptoms  marked  systemic  depression  or  abnormal 
symptoms  of  the  kidneys,  the  digestive  tract,  or  of  other  parts  of 
the  body.  Likewise,  the  cases  grouped  under  the  heading  "  Col- 
lapse "  often  present  also  cutaneous  or  other  symptoms.  In  spite 
of  the  difficulty  of  classifying  the  cases  accurately,  however,  it  is 
believed  that  the  method  possesses  distinct  advantage  over  a  mere 
alphabetical  or  chronological  classification.  The  references  are  ar- 
ranged alphabetically  and  chronologically  under  each  heading. 

The  total  number  of  cases  of  poisoning  by  antipyrin  herein  re- 
corded is  approximately  488.  As  already  stated,  it  is  practically 
impossible  to  determine  the  number  of  cases  with  accuracy,  owing 
to  the  indefinite  character  of  some  of  the  reports.  The  cases  were 
reported  by  299  observers.  Of  the  488  cases  10,  or  about  2  per  cent, 
are  reported  to  have  resulted  fatally.  The  distribution  of  the  re- 
corded cases  by  years  from  the  time  of  the  introduction  of  antipyrin 
as  a  medicinal  agent,  in  1884,  to  the  end  of  the  year  1907,  is  shown  in 
the  accompanying  table. 

Cases  of  antipyriyi  poisoning  reported  annually. 


Year. 

Number 
of  cases 
reported. 

Number 
of  ob- 
servers. 

Year. 

Number 
of  cases 
reported. 

Number 
of  ob- 
servers. 

Year. 

Number 
of  cases 
reported. 

Number 
of  ob- 
servers. 

1884 

1885 

1886 

1887 

1888 

1889 

1890 

33 

68 
48 
37 
55 
24 
22 
12 
34 

19 

28 
18 
27 
41 
18 
8 
11 
11 

1893 

1884 

1895 

1896 

1897.. 

1898 

1899 

1900 

1901 

13 
16 
28 
13 
31 
22 
2 
0 
1 

10 

16 

17 

13 

20 

11 

2 

0 

1 

1902 

1903 

1904 

1905 

1906 

1907 

Total. 

4 
8 
7 
3 
6 
2 

4 
8 
6 
3 
5 
2 

1891 

1892 

488  1              299 

LITERATURE    ON    ANTIPYRIN    POISONING.  47 

These  figures  indicate  either  that  there  has  been  a  considerable 
falling  off  in  the  use  of  antipyrin  during  recent  years,  or  that  the 
drug  has  been  employed  with  greater  caution  and  discrimination, 
and  undoubtedly  both  of  these  factors  have  played  an  important  part 
in  reducing  the  number  of  cases  of  poisoning.  The  inefficiency  of 
the  drug  in  the  treatment  of  some  of  the  affections  for  which  it  was 
formerly  reconnnended  and  the  uncertainty  of  the  effect  of  its  admin- 
istration may  have  contributed  to  this  decrease.  A  review  of  the 
cases  herein  recorded  will  show  that  in  a  number  of  instances  a  single 
dose  of  antipyrin  of  .")  grains  or  less  has  produced  alarming  symptoms 
in  adults,  while  a  dose  of  10  or  15  grains  has  produced  serious  col- 
lapse. In  many  cases  of  harmful  results  the  dose  appears  to  have 
been  neither  unduly  large  nor  too  long  continued,  and  there  seems  to 
have  been  little,  if  any,  direct  relation  between  the  size  of  dose  and 
the  occurrence  and  severity  of  the  ill  effects.  Furthermore,  untoward 
symptoms  have  appeared  so  promptly  in  many  cases  as  to  lead  soine 
observers  to  believe  that  the  manifestations  are  largely  reflex  in 
character,  inasmuch  as  there  appeared  to  be  almost  no  time  allowed 
for  absorption  of  the  drug  from  the  stomach  between  the  time  of 
ingestion  and  the  appearance  of  the  symptoms.  This  uncertainty'  of 
results  has  undoubtedly  been  an  important  factor  in  bringing  about  a 
more  conservative  use  of  the  drug. 

ABSTRACTS  OF  ANTIPYRIN  CASES. 
CUTANEOUS   MANIFESTATIONS. 

Under  this  heading  are  grouped  the  recorded  cases  of  antipyrin 
poisoning  in  which  the  cutaneous  .symptoms  appear  to  have  occupied 
the  most  important  place  in  the  clinical  history.  They  are,  how- 
ever, not  necessarily  the  only  ones  described  in  the  published  reports, 
and  cutaneous  manifestations  are  recorded  in  many  of  the  cases 
which  have  been  grouped  under  other  headings. 

A  review  of  the  reported  cases  shows  that  the  cutaneous  symptoms 
presented  themselves  most  often  in  the  form  of  a  rash  or  eruption, 
often  accompanied  by  swelling  and  severe  itching.  The  eruption 
appeared  in  widely  different  forms,  and  varied  much  in  the  different 
cases  as  regards  character,  time  of  appearance,  duration,  part  of 
the  body  affected,  severity,  etc.  The  form  which  appears  to  have 
been  observed  most  frequently  was  that  of  urticaria,  accompanied  by 
severe  itching.  In  other  cases  the  eruption  resembled  that  of  scarlet 
fever,  in  others  that  of  measles,  and  in  .still  others  that  of  herpes, 
eczema,  or  pemphigus.  In  most  of  the  cases  the  symptoms  appeared 
promptly  after  the  ingestion  of  one  or  two  doses  of  the  drug;  in 
some,  however,  they  were  delayed,  and  in  not  a  few  instances  the 
cutaneous  manifestations  did  not  make  their  appearance  until  after 


48  ACETANILID,    ANTIPYEIN,    AND   PHENACETIN. 

the  drug  had  been  taken  in  fairly  large  doses  for  days.  Whether  they 
appeared  early  or  late,  the  symptoms  usually  came  suddenly  and  lasted 
only  a  few  hours,  with  the  exception  of  two  or  three  cases,  when  they 
continued  for  several  days.  In  not  a  few  instances  their  disappear- 
ance was  followed  by  desquamation.  The  distribution  of  the  erup- 
tion presented  many  variations.  In  some  of  the  cases  it  appears  to 
have  affected  the  skin  of  the  entire  body,  while  in  others  it  attacked 
only  a  comparatively  small  area — for  instance,  the  back  of  the  hand 
or  knee.  In  the  mild  cases  the  eruption  was  a  mere  erythematous 
blush,  causing,  however,  much  discomfort;  but  in  the  severe  cases 
the  skin  was  red,  swollen,  and  hot,  and  the  sensation  of  heat  and  itch- 
ing was  distressing. 

Besides  an  eruption,  the  skin  manifestations  in  poisoning  by  anti- 
pyrin  included  edema.  The  swelling  in  most  cases  affected  first  the 
face,  especially  the  skin  around  the  eyes,  and  the  statement  frequently 
occurs  in  the  reports  that  the  patient's  face  became  so  swollen  that 
he  was  unrecognizable.  The  swelling  in  not  a  few  instances  involved 
the  skin  of  the  entire  body.  Cyanosis  was  observed  in  only  two  or 
three  cases,  and  pruritus  without  the  appearance  of  a  rash  in  a  very 
few  instances. 

Alexander.     Zweiter   Bericht  iiber   die  Wirkungen   und   Nebenwirkungen   des 
Antipyrins.     Breslau  arztl.     Zts.,  1884,  6:  169. 

Four  cases  of  typhoid  fever  in  wliich  ttie  administration  of  antipyrin 
was  followed  by  the  appearance  of  an  eruption. 

BiELSCHOWSKY,  E.     Beitrage  zur  Antipyrin-Behandlung.     Breslau.  arztl.     Zts., 
1884,  6:  193. 

Two  cases  of  typhoid  fever  in  which  the  administration  of  antipyrin 
was  followed  in  one  case  by  an  erythematous  eruption  and  in  the  other 
by  collapse. 

Cahn,  A.    Ueber  Antipyrin  und  Antipyrinexanthem.    Berl.  klin.     Wochenschr., 
1884,  21:  569. 

Two  cases,  one  of  typhoid  fever  and  the  other  of  phthisis,  in  which  the 
ingestion  of  antipyrin  was  followed  by  the  appearance  of  an  erythematous 
rash. 

Debove,  cited  by  Denux,  M.     Etude  sur  la  valeur  th^rapeutique  de  I'antipyrine. 
Paris,  1884. 

Ingestion  of  antipyrin  was  followed  by  the  appearance  of  a  morbilliform 
eruption. 

Demme,  R.     Physiologische  und  therapeutische  Beitrage  zur  Kenntnis  des  Anti- 
pyrins.    Fortschr.  d.  Med.,  Berlin,  1884,  2:  689. 

Two  cases  in  children,  one  of  acute  rheumatism  and  the  other  of  typhoid 
fever,  in  which  the  administration  of  antipyrin  was  followed  in  one  case 
by  the  appearance  of  an  erythematous  rash,  and  in  the  other  by  symptoms 
of  marked  depression. 


LITERATURE    ON    ANTIPYRIN    POISONING.  49 

DoEBNER.     Ein  Autipyrinausschlag.     Aerztl.  Int.-Bl.,  Miinchen,  1884,  31:  571. 

Woman,  28  phthisis.  After  the  ingestion  of  3.25  drachms  of  autipyriu 
during  twelve  days,  a  morbilliform  eruption  made  its  appearance. 

Ernst,  P.     Antipyrinexanthem.     Centrbl.  klin.  Med..  Leipzig.  1884,  5:  521. 

Two  cases  of  typhoid  fever  in  which  the  administration  of  antipyrin  was 
followed  by  an  eruption  upon  the  skin. 

Geier,  a.    Zur  AA'irkung  des  Antipyrin  bei  Kindern  und  Erwachsenen.   Deutsche 
med.     Wochenschr.,  1884,  10:  730. 

Man,  39,  typhoid :  After  taking  antipyrin  for  nine  days  an  erythematous 
rash  appeared.    Erythema  on  back  and  extremities. 

Meissen.     Antipyrin  bei  Fhthise.     Deutsche  med.     Wochenschr.,  Berlin,  1884, 
10:  827. 

An  eruption  appeared  immediately  after  resuming  the  use  of  antipyrin, 
after  an  interval  of  eight  days. 

Pribram,  A.     Ueber  das  Antipyrin.     Prag.  med.  Wochenschr.,  1884,  9:  422. 

In  four  cases,  erythema  followed  the  use  of  antipyrin  for  three  days  in 
doses  of  15  and  30  grains.  In  a  case  of  tuberculosis,  collapse  occurred 
after  the  injection  of  1  drachm  of  antipyrin. 

Rank,  C.     Ueber  den  therapeutischen   Werth  des  Antipyrins.     Deutsche  med. 
Wochenschr.,  Berlin,  1884,   10:  .373. 

The  injection  of  antipyrin  was  followed  by  an  eruption  resembling  urti- 
caria. 

Secchi.     Zur  Wirkung  des  Antipyrin  bei  Phtliise.     Exanthem  nach  Anwendung 
desselben.     Breslau.  iirztl.  Zts..  1884.  6:  184. 

In  two  ca.ses  a  morbilliform  eruption  with  severe  itching  followed  the  in- 
gestion of  1.5-grain  doses  of  antipyrin. 

SuNEB,  E.     Mas  sobre  la  antipirina.     Genio  med.-quir.,  Madrid,  1884,  30:  494. 

Erythema  with  severe  itching  appeared  on  the  fourth  day,  after  the  in- 
gestion of  45  grains  of  antipyrin. 

Wising,    P.    J.     Om    biverkningar    af    antipyrin.     Ilygiea,    Stockholm.     1884, 
46:  716.    Abs.  Lancet,  London,  1887.  2:  85. 

A  rash  of  bluish-red  spots  on  the  face  following  the  ingestion  of  anti- 
pyrin. 

1>-IM.~>. 

DK  Gassicourt,   C.     Discussion   of   i)aper  l)y   Doscroizilles.      L'emploi  de   I'anti- 
pyrine  chez  les  enfants.     .1.  mC'd.,  Paris,  1885,  8:  91 L 

Two  eases  In  which  the  ingestion  of  antipyrin  was  followed  by  the  ap- 
pearance of  an  eruption  of  bright  red  spots. 

Dkai'kk,  \V.  II.     Aniipyrin  and  its  effects.     .Med.  liec,  New  York.,  188.5,  27:  414. 
An  erujition  n'scnibling  that  of  measles  occurred  in  G  out  of  20  cases  of 
typhoid   tr('ale<l   witii  jiiilipyrin. 

Keknaout,  E,     Essal  snr  riictioM  d<^  r:ni1i|)yrin»>  dans  l;i  (ir-vrc  fypliuVdc.     I'aris, 
188.5. 

A   roseola   followed  tli<-  iHoiongcMl   use  of  antipyrin   in   lyplioid  fever. 

82.310— Bull.  i2*>—(y.) i 


50  ACETANILID,    ANTIPYEIN,    AND    PHENACETIN. 

GiORGiEKi,  C.  Suir  eruzione  cutanea  per  1'  uso  dell'  antlpirina.  Gazz.  med.  ital. 
lomb.,  Milano,  1885   (8.  s.),  7:  273. 

Two  cases  in  which  an  eruption  followed  the  ingestion  of  antipyrin. 

GuTTMANN,  P.  Ueber  antipyretische  Mittel.  Berl.  kiln.  Wochenschr.,  1885,  22 : 
401. 

In  6  cases  out  of  297  an  exanthematous  eruption  followed  the  ingestion 
of  antipyrin. 

Kaatzer.  p.  Antipyrin  bei  Phthisis.  Deutsche  med.  Wochenschr.,  Berlin,  1885, 
11:  270. 

In  2  cases  the  ingestion  of  antipyrin  was  followed  by  the  appearance  of 
an  exanthematous  eruption. 

PtJSiNELLi.  Ueber  Antipyrin.  Deutsche  med.  Wochenschr.,  Berlin,  1885, 
11:  145. 

In  7  cases  of  typhoid  the  ingestion  of  antipyrin  was  followed  by  the  ap- 
pearance of  an  exanthematous  eruption. 

RoLLET,  M.  F.  Note  sur  Tantipyrine  chez  les  tuberculeux.  Lyon  med.,  1885, 
49:  453. 

An  eruption  appeared  in  1  out  of  5  cases  of  tuberculosis  treated  with 
antipyrin. 

Roux-Seignoret.  Sur  un  cas  de  fievre  typlioi'de,  traite  par  Tantipyrine.  Erup- 
tion rubeoliforme  au  dixieme  jour.     France  med.,  Paris,  1885,  2 :  921. 

Typhoid :  The  ingestion  of  antipyrin  was  followed  on  the  tenth  day  by 
the  appearance  of  a  morbilliform  eruption,  covering  the  entire  body. 

Sartorius,  E.    Antipyrin  in  der  Kinderpraxis.     Erlaugen,  1885. 

Child,  6 :  Ingestion  of  antipyrin  was  followed  by  the  appearance  of  an 
exanthematous  eruption. 

Secretan,  L.  Antipyrine  et  rhumatisme.  Rev.  med.  Suisse  Rom.,  Geneve, 
1885,  5:  718. 

The  ingestion  of  antipyrin  was  followed  by  the  appearance  of  a  morbilli- 
form eruption,  covering  the  entire  body. 

Shattuck.  G.  B.  The  results  of  the  use  of  antipyrine  at  the  Boston  City 
Hospital.     Boston  Med.  and  Surg.  J.,  1885,  113:  78. 

In  a  small  proportion  of  cases  the  exhibition  of  antipyrin  was  followed 
by  the  appearance  of  an  eruption. 

Welt,  S.  Klinische  Beobachtungen  fiber  die  antifebrile  Wirkung  des  Anti- 
pyrins  und  Thallin  nebst  Bemerkungen  iiber  individuelle  Antipyrese. 
Deutsches  Arch.  klin.  Med.,  Leipzig,  1885-6,  38:  81. 

Thirteen  out  of  122  patients  treated  with  antipyrin  developed  an  ery- 
thema. 

Ziteke,  J.  X.     Antipyrine.     Therap.  Gaz.,  Detroit,  1885  (3.  s.),  1:  517. 

Author  observed  cases  in  which  exanthematous  eruptions  followed  the 
prolonged  use  of  antipyrin. 

18S6. 

Blomfield,  J.  E.  Two  cases  of  antipyrin-rash.  Practitioner,  London,  1SS6, 
36:  261. 

Two  cases  of  acute  phthisis  in  which  the  ingestion  of  from  7  to  12  grains 
of  antipyrin  3  times  daily  was  followed  by  the  appearance  of  an  eruption 
upon  the  skin. 


LITERATURE    OX    AXTIPYRIN    POISONING.  51 

Cattani.    G.    Deir    esautema    antipiriuico.     Gior.    ital.    d.    mal.    ven.,    Milauo, 

Six  cases  in  which  an  eruption  followed  the  ingestion  of  antipyriu. 

DE  Renzi.  E.     Eruzione  cutanea  prodotta  dall'  antipirino.     Kiv.  clin.  e  teran 
Xapoli,  1886,  8:  57.     • 

Male,  typhoid:  Ingestion  of  4.5  drachms  of  autipyrin  within  three  days 
was  followed  by  an  erythematous  eruption. 

Fraenkel.    a.     Ueber    Antipyrinbehandlung    des   acuten    Gelenkrheumatismus. 
Deutsche  med.  Wocheuschr.,  188(5,  12:  772. 

Man,  39,  articular  rheumatism  :  The  ingestion  of  1.25  drachms  of  anti- 
pyriu daily  for  six  days  was  followed  by  the  appearance  of  an  erythema 
covering  the  entire  body. 

Fraxkenbehg,  J.  H.     Antipyriue.     Med.  Rec,  New  York,  1886,  29:  585. 

Seven  cases  in  which  the  ingestion  of  antipyriu  was  followed  by  an 
eruption  on  the  skin.  In  one  the  quantity  taken  was  5  drachms  within 
two  weeks  in  15-grain  doses.  In  the  other  the  quantity  was  1  to  3  ounces 
in  the  same  period  of  time. 

Fruitnight,    J.    H.     Kairine    and    antipyrine.     Med.    Rec,    New    York,    1886, 
29:  647. 

Acute  phthisis :  Five  grains  of  autipyrin  given  every  four  hours  pro- 
duced a  bright  red  miliary  eruption. 

GoLBiEwsKi.  E.     Feber  die  Wirkung  von  Antipvrin  bei   Gelenkrheumatismus. 
Berl.  kliu.  \Vochenschr.,  1886,  23:  463. 

In  about  70  cases  there  wore  only  2  instances  in  which  an  exanthem  re- 
sembling urticaria  followed  the  use  of  antipyrin. 

Laache,  S.     Ein  Fall  von  •'  kontrJirer  "  Antipyrinwirkung.     Centrbl.  klin.  Med., 
Leipzig,  1886,   7:  .545. 

Man.  phthisis:  The  ingestion  of  0.5  drachm  dose  of  autipyrin  was  fol- 
lowed by  a  chill  and  rise  of  temperature.  On  the  next  day  a  scarlatiniform 
eruption  appeared  upon  the  skin. 

Laube.     l^ltude  clinique  sur  la  valeur  de  I'antipyriue  specialement  appliquee  a, 
la  therapeutique  infantile.    Rev.  mens.  mal.  I'enf.,  Paris,  1886,  4:  57. 

On  four  occasions  a  morbilliform  eruption  was  observed  in  children  fol- 
lowing the   ingestion  of  antipyrin. 

-Masius  et  Snyers,  p.     Contribution  a  I'etude  do  riintipyrin(>.     Hul.  Acad.  roy. 
xnM.  Relg.,  Bruxelle.s,  1886  (3.  s.),  20:  547. 

Case  in  which  an  exanthematous  eruption  followed  thi'  ingestion  of  anti- 
pyrin. 

Dau.v.  E.  ().     Rash  produced  by  antipyrin.     I'.rit.  .Med.  .1.,  London,  1887,  1:  111. 
Two  cases   in  which  a   morbilliform  eruption   followed  the  ingestion  of 
antiityrin. 

IIaykm.     MfMles  diKlniinistratioii  df  riiiitipyrine.     J.  nu'd.  I'ai-is,  1S87,  12:  708. 
Ingestion  of  0.5  «lra(lnii  of  anli|iyrin  gave  rise  to  an  inlcnse  crylliema. 

IIayh,  .7.   M.     SIrtugbing  following  a    liypodennie   injefljoii   of  iintiiiyiin.      .Med. 
Iter;.,  New  York,  1887,  «2:  486, 

Inje^'tion  of  12  grains  of  antipyrin  dissolved  in  water  was  followed  by  a 
severe  urticarial  eruption,  and  a  slough  the  size  of  u  silver  quarter. 


52  ACETANILID,   ANTIPYEIN,   AND   PHENACETHST. 

JozEFOWicz.     On  the  antipyrin  rash.     Proceedings  of  the  Kovno  Medical   So- 
ciety, 1886,  No.  2,  p.  17  (Abs.  Lond.  Med.  Record,  1887,  15:  264). 

Two  cases  of  exanthem  following  the  ingestion  of  antipyrin,  one  with 
and  the  other  without  severe  itching. 

Leitzmann,  G.     Eine  Nebenwirkung  des  Antipyrin.     Berl.  klin.   Wochenschr., 
1887,  24:  531. 

Woman,  pneumonia :  A  dose  of  15  grains  of  antipyrin  was  followed  in 
four  hours  by  a  chill  and  vomiting,  and  later  by  an  erythema. 

Martini,  V.     Orticaria  per  antipirina.     Boll.  d.  sez.  d.  cult.  d.  sc.   med.  n.  r. 
accad.  d.  flsiocrit.  di  Siena,  1887,  5:  114. 

Urticaria  and  intense  itching  followed  the  ingestion  of  antipyrin. 

Paget,  W.  S.     Rash  produced  by  antipyrin.     Brit.  Med.  J.,  London,  18S7,  1 :  210. 

The  ingestion  of  antipyrin  for  eight  days  on  an  average  of  1  drachm 
daily  was  followed  by  the  appearance  of  a  bright  red  rash. 

SCHWARZ.     Ein  Fall  von  Antipyrinexanthem.     Miinch.  med.  Wochenschr.,  1887, 
34:  59. 

Woman,  27,  typhoid  :  Ingestion  of  9  drachms  of  antipyrin  in  fourteen  days 
was  followed  by  a  severe  chill  and  then  by  a  m'orbilliform  rash  with  severe 
itching. 

StE,  G.     De  I'antipyrine  contre  la  douleur.     Compt.  rend.  acad.  sci.,  Paris,  1887, 
104:  1085. 

Author  had  observed  an  eruption  resembling  that  of  scarlatina  or  urti- 
caria following  the  ingestion  of  antipyrin  in  doses  of  from  1  to  1.5  drachms 
daily. 

Spitz,  B,     Ein  eigenthiimlicher  Fall  von  Dermatitis  hervorgerufen  durch  Anti- 
pyrinbehandlung.     Therap.  Monatsh.,  Berlin,  1887,  1 :  347. 

Girl,  20,  typhoid :  One-half  drachm  doses  of  antipyrin  were  followed  by  a 
morbilliform  rash  with  subsequent  desquamation. 

Victor,  P.    Antipyrin  rash.     Indian  Med.  Gaz.,  Calcutta,  1887,  22:  241. 

Boy,  14,  typhoid :  Between  June  26  and  July  6  received  300  grains  of  anti- 
pyrin. A  vesicular  and  papular  rash  appeared  over  the  whole  body,  and 
lasted  six  days. 

Whitehouse,  J.  S.    A  case  of  antipyrin  poisoning.     Med.  Rec,  New  York,  1887, 
32:  706. 

The  ingestion  of  7.5  grains  of  antipyrin  was  followed  in  two  minutes  by 
severe  gastric  pain  and  soon  after  by  the  appearance  of  an  urticarial  erup- 
tion and  symptoms  of  collapse. 

ISSS. 

Barber,  C.  F.     Some  toxic  effects  of  autipyrine.     Med.  Rec,  New  York,  1888, 
33:   14. 

Ingestion  of  15  grains  of  antipyrin  was  followed  by  the  appearance  of 
an  urticarial  eruption  with  intense  itching.     The  face  was  much  swollen, 
*      features  being  obliterated. 


LITERATURE    ON    ANTIPYRIN    POISONING.  53 

BoKENHAM,  T.  J.     Some  therapeutic  uses  of  antipyrin.     Practitioner,  London, 
1888,  40:  266. 

(1)  Ingestion  of  20  grains  of  antipyrin  3  times  a  day  for  fourteen  days 
by  a  child  was  followed  bj-  malaise  and  the  appearance  of  an  eruption 
resembling  that  of  both  urticaria  and  scarlatina.  (2)  Ingestion  of  an- 
tipyrin   was    followed    by    drowsiness,    vertigo,    delirium,    and    diarrhea. 

(3)  The  first  dose  of  antipyrin  was  followed  by  symptoms  of  depression. 

(4)  Antipyrin  caused   the  appearance  of  a   rash   like  that   described   in 
case  1. 

Cehak.     Zur  Wirkung  des  Antipyrins.    AUg.  Wien.  med.  Ztg.,  1888,  33:  316. 

Ingestion  of  15  grains  of  antipyrin  was  followed  by  severe  sneezing, 
dyspnea,  and  swelling  of  the  entire  face  and  inside  of  the  mouth.  In  2 
cases  erythema  followed  the  ingestion  of  antipyi'in. 

Clabemont,  C.  C.     Antipyrin  rashes.     Brit.  Med.  J.,  London,  1888,  2 :  943. 

In  2  cases  an  eruption  followed  the  ingestion  of  antipyrin  in  tj^phoid 
fever. 

DuRAND,    .J.     Eruption     scarlatiniforme    causee     par     I'antipyrine.     Gaz.    hop. 
Toulouse,  1888,  2:  225. 

Man,  55,  neuralgia  :  A  scarlatiniform  eruption  followed  the  ingestion  of 
0.5  drachm  of  antipyrin. 

DuTT,  U.  K.     Idiosyncrasy  with  regard  to  antipyrin.     Brit.  Med.  J.,  London, 
1888,   1:  1147. 

Ingestion  of  antipyrin  was  followed  by  violent  itching,  tingling,  and 
burning  of  the  throat  and  skin,  and  sneezing.     No  eruption. 

Gbognot.     Sur  un  cas  d'oedeme  oonseoutif  a  I'absorption  de  I'antipyrine.     Bui. 
gen.  therap.  [etc.],  Paris,  1888,  115:  134. 

Man,  35,  facial  neuralgia :  Fifteen  minutes  after  taking  15  grains  of 
analgesin,  edema  of  the  face  developed. 

Habdy.     Sur  I'emploi   therapeutique  de  I'antipyrine  et  de  I'acStanilide.     Bui. 
Acad,  med.,  Paris,  1888   (2.  s.),  19:  245. 

Man,  30 :  Developed  a  scarlatiniform  eruption  after  taking  antipyrin. 

Jennings,  O.    On  poisoning  by  antipyrin.    Lancet,  London,  1888,  1:  3(54. 

(1)  Ingestion  of  2.5  grams  of  antipyrin  daily  for  eight  days  was  fol- 
lowed by  the  appearance  of  an  eruption  over  the  whole  body,  swelling  of 
the  face,  symptoms  of  collapse  and  prostration.  (2)  Young  woman  took 
5  grams  of  antipyrin  a  day  for  rheumatism.  On  the  second  day  she  was 
found  .swaying  back  and  forth,  and  repeatedly  crying  that  she  had  lost  her 
memory  and  was  going  mad.  She  subsequently  had  an  attack  of  gastro- 
enteritis, (3)  Woman.  The  ingestion  of  aiitii)yrln  was  followed  by  a 
swelling  of  the  body,  dysimea,  and  the  appearance  of  an  erniilion. 

Lanpheak,  E.     a  pet-uliar  effect  of  aiitii)yriM.     KansMs  City  Med.   Index,  1888, 
9:  155. 

Woman,  52:  Ingestion  of  1.5  ounces  of  antiiiyrln  in  one  week  was  on 
2  occasions  followed  by  deep  cyanosis  and  swelling  <>f  th<>  f>ici>  and 
extremities. 


54  ACETANILID,   ANTIPYEIN,   AND   PHENACETIN. 

Macdonald,  a.  Antipyrin  and  idiosyncrasy.  Brit.  Med.  J.,  London,  1888, 
1:  296. 

Girl,  typhoid :  Ingestion  of  3  doses  of  antipyrin  daily  for  twelve  days  was 
followed  by  the  appearance  of  an  urticarial  eruption  over  the  entire  body 
except  the  face. 

Mahnert,  F.  Studien  und  Erfahrungen  iiber  Antipyrin.  Mittheil.  Ver.  Aerzte 
in  Steiermark,  1888,  24:  62. 

Author  states  that  he  had  seen  but  1  case  in  which  a  morbilliform  rash 
followed  the  ingestion  of  antipyrin. 

Mayet.     Bui.  mem.  soc.  de  therap.,  Paris,  1888  (2.  s.),  15:  33. 

Ingestion  of  45  grains  of  antipyrin  was  followed  by  an  intense  urticarial 
eruption ;  7.5  grains  taken  later  caused  swelling  of  the  eyelids  and  entire 
face. 

Mazzotti,  L.  Esantema  antipirinico  per  iniezioni  sottocutanee  d  "antipirina  ed 
eruzione  di  herpes  zoster  sopra  di  esso.  Gior.  ital.  mal.  ven.,  Milano,  1888, 
23:  210. 

An  eruption  followed  the  subcutaneous  injection  of  antipyrin. 

Oliver,  T.  Clinical  experience  of  some  of  the  more  I'ecently  introduced  drugs. 
Lancet,  London,  1888,  1:  868. 

A  herpetic  eruption  followed  the  ingestion  of  antipyrin  taken  for  neu- 
ralgia. 

Ollivier,  a.     Bui.  Acad,  med.,  Paris,  1888  (2.  s.),  19:  229. 

Child,  chorea :  Ingestion  of  antipyrin  was  followed  by  the  appearance  of 
an  erythematous  rash. 

Ory.  Contre-indications  de  I'antipyrine,  son  emploi  dans  la  polyurie.  J.  m^d. 
Paris,  1888,  14:  486. 

Forty-five  grains  of  antipyrin  taken  during  the  day  gave  rise  to  a  miliary 
eruption  over  the  entire  body. 

Stack,  J.  J.     Antipyrin.     Lancet,  London,  1888,  2:  1112. 

On  3  occasions  the  ingestion  of  a  10-grain  dose  of  antipyrin  caused  the 
appearance  of  an  urticarial  eruption  over  the  entire  body  with  itching 
and  a  disagreeable  sense  of  uneasiness. 

TisNE.     Eruption  due  a  I'usage  de  I'antipyrine.     J.  med.  Paris,  1888,  15:  327. 
The  ingestion  of  antipyrin  was  followed  by  the  appearance  of  a  scarlatini- 
form  eruption. 

Wilson,  J.  C.  Note  on  antipyrin  as  an  analgesic.  J.  Nerv.  Ment.  Dis.,  New 
York,  1888  (n.  s.),  13:  42. 

In  two  or  three  instances  a  transient  scarlatiniform  eruption  followed 
the  use  of  antipyrin. 

WiNDELSCHMiDT.  Ueber  die  Wirkung  des  Antipyrin  bei  der  Menstruationscolik, 
Allg.  med.  Centr.-Ztg.,  Berlin,  1888,  57:  1029. 

Boy,  7 :  A  dose  of  4.5  grains  of  antipyrin  was  followed  by  the  appearance 
of  an  urticarial  eruption  and  high  fever. 


LITERATURE   ON   ANTIPYRIN   POISONING.  55 

1S89. 

Amon.   H.     Subkntane  Antipyrin-Injektion   bei  akxitein    (ielenksrheumatismus. 
Interuat.  kliu.  Kimdscliuvi,  Wien,  ISS9,  3:  123. 

A  small  superficial  patch  of  gangrene  of  the  skiu  followed  the  subcutane- 
ous injection  of  antipyrin. 

Boucher.     Eruption   due  a  I'antipvrine.     Bull.   soc.   med.   Rouen,    (1889)    1890 
(2.  s.),  3:  29. 

A  morbilliform  eruption  followed  the  ingestion  of  antipyrin. 

Gkandclement.      Indications    et   dangers   de   I'antipyrine.     Lyon    med.,    1889, 
60:  414. 

Man,  G5 :  One  or  2  doses  of  antipyrin  of  7.5  grains  each  were  followed 
by  the  appearance  of  an  eruption  upon  the  skin.  It  reappeared  every 
time  the  patient  took  antipyrin. 

Ferret.    S..   and  Devic,   E.     Des  eruptions   rubeoliformes  dues  h  I'antipyrine. 
Province  med.,  Lyon,  1889,  3:  301. 

Girl,  5:  A  morbilliform  eruption  follow^ed  the  ingestion  of  antipyrin. 

Watkins.  W.     Antipyrin  ;  results  following  its  administration.     Lancet,  London, 

1889,  2:  903. 

Woman.  37,  headache :  A  dose  of  10  grains  of  antipyrin  was  followed  by 
great  swelling  of  the  upper  lip. 

1890. 

Dubousquet-Laborderie.     Traitement   de   la    coqueluehe   par   I'antipyrine.     Se- 
maine  med.,  Paris,  1890,  10:  154. 

Ill  effects  were  noted  in  15  out  of  300  cases  treated  with  antipyrin,  prin- 
cipally a  scarlatiniform  eruption  or  gastric  disturbance. 

Lewis.  D.  C.     Five  hours  with  15  grains  of  antipyrine.     Med.  Brief,  St.  Louis, 

1890,  18:  282. 

Half  an  hour  -after  taking  15  grains  of  antipyrin  the  patient's  face  be- 
came swollen,  the  sight  blurred,  the  hearing  indistinct,  and  an  urticarial 
eruption  made  its  appearance. 

1891. 

de    MOLfeNES,    P.     Ervthr-mc    antipyrhiiquo.     Ann.    derniat.    syph.,    Paris,    1891 
(3.  s.),  2:  384. 

An  erythematous  cruiitioii  lasting  aliout  six  days  followed  the  ingestion 
of  antipyrin. 

Gliazstein,   I.     K.   Kazuist   t.  n.   lekarst.   sypei.      (So-called  drug  exanthem). 
Meditsina,  St.  Petersburg,  1S91,  3:  405.     Cited  by  Fournier,  1892,  p.  490. 

(1)  An  erythematous  eruption  fcjllowed  the  ingestion  of  7.5  grains  of 
antipyrin.  SubscnpuMitly  another  dose  of  the  drug  was  followed  l)y  similar 
symptoms.  (2)  On  2  occasions  an  eruption  ai)iieared  after  the  ingestion 
of  3  doses  of  aii1ii»yrin.  2.5  grains  eafli,  in  the  case  <if  a  cliild. 

Gkanciikr.     Eruption    IVi)rile   due   il    I'antipyrine.     .1.    med.    cliir.    prat.,    Paris, 

1891,  «2:  3:M. 

Child  for  «'ig]it  days  was  given  .37.5  grains  of  antipyrin  daily.  Tliis  was 
followed  by  a  morbilliform  rash  with  fever.  II  disappeared  two  days  after 
the  drug  was  dlHcoutluued,  and  reui)i)eared  when  It  was  again  taken. 


56  ACETANILID,   ANTIPYEIN,   AND   PHENACETIN. 

Laloy,   L.     Deux   cas  d'exantbeme  par  absorption  de   substances   medicamen- 
teuses.     J.  med.  cbir.  prat.,  Paris,  1891,  62:  921. 

Woman,  45,  beadacbe :  A  dose  of  15  grains  of  antipyrin  was  followed 
by  tbe  appearance  of  a  morbilliform  rasb. 

189  S. 

Gaspary.     Ueber  Arzneiausschlage.     Monatsb.  prakt.  Dermat.,  Hamburg,  1892, 
14:  326. 

Five  cases  in  whicb  eruption  followed  tbe  ingestion  of  antipyrin. 

EiCHHORST,  H.     Zur  Kenntniss  des  Antipyrinexantbems.     Tberap.     Monatsb., 
Berlin,  1892,  6:  381. 

Two  cases  of  typboid  in  wbicb  tbe  administration  of  antipyrin  was 
followed  by  tbe  appearance  of  an  eruption. 

FouRNiER,    H.     Notes    pour    servir    S,    I'etude    des    eruptions    determinees    par 
I'antipyrine.     J.  mal.  cutan.  sypb.,  Paris,  1892,  4:  488. 

Four  cases  in  wbicb  an  eruption  followed  tbe  administration  of  anti- 
pyrin. 

Lemonnier.     Erytbeme  scarlatiniforme  du  a  I'antipyrine.     Ann.  dermat.  sypb., 
Paris,  1892  (3.  s.),  3:  734. 

An  erytbema  appeared  two  bours  after  tbe  ingestion  of  antipyrin. 

Leroux,  cited  by  Fournier,  1892,  p.  499. 

In  16  cases  an  eruption  followed  tbe  ingestion  of  antipyrin  in  cborea. 

MoELLER,     J.     Zur     Kenntniss     des     Antipyrinexantbems.     Tberap.     Monatsb., 
Berlin,  1892,  6:  580. 

A  dose  of  15  grains  of  antipyrin  was  followed  by  tbe  appearance  of  an 
erytbematous  eruption,  witb  swelling  of  tbe  lips,  nose,  and  eyes. 

Petrini.     Eruption    pempbigoide    antipyrinique.     Ann.    dermat.    sypb.,    Paris, 
1892  (3.  s.),  3:  170. 

A  pempbigoid  eruption  followed  ingestion  of  antipyrin. 

Short,  T.  S.     On  tbe  toxic  effects  of  antipyrin.     Birmingbam  Med.  Rev.,  1892, 
31:  340. 

On  tbree  occasions  tbe  ingestion  of  a  5-grain  dose  of  antipyrin  was 
followed  by  redness  and  swelling  of  tbe  face,  tbe  appearance  of  a  scarlatini- 
form  rasb  and  tbe  formation  of  ulcers  in  tbe  moutb. 

1893. 

Childe,  C.  p.     Rasb  caused  by  taking  antipyrin.     Brit.  Med.  J.,  London,  1893, 
2:  944. 

On  four  occasions  tbe  ingestion  of  antipyrin  was  followed  by  tbe  appear- 
ance of  an  eruption. 

Freudenberg,  a.     Oedematose  Scbwellung  des  Praeputium  als  Nebenwirkung 
des  Antipyrin.     Centrbl.  klin.  Med.,  Leipzig,  1893,  14:  97. 

Man,  30:  A  dose  of  7.5  grains  of  antipyrin  was  followed  by  a  sensation 
of  burning  in  tbe  uretbra  and  itcbing  and  swelling  of  tbe  prepuce. 

Leviseur.     Discussion  of  Pollitzer's  case  (1893).    New  Yorker  med.  Monatsscbr., 
1893,  5:  519. 

A  ease  similar  to  tbe  one  described  by  Pollitzer  (1893),  in  wbicb  7.5 
grains  of  antipyrin  were  taken. 


LITERATURE    ON    ANTIPYRIX    POISONING.  57 

PoLLiTZER.     Eiue   seltenere   Form   vou  Antipyriuexanthem.     New  Yorker   med. 
Mouatsschr.,  1893,  5:  519. 

Ingestion  of  30  grains  of  antipyrin  within  two  hours  caused  swelling  of 
the  lips  and  tongue  and  the  appearance  of  a  vesicular  eruption  upon  the 
face,  dorsum  of  the  hand,  and  glans. 

1894. 

Benzler.     Ueber    Arzneiexanthem    besonders   nach   Antipyrin,      Deutsche    mil. 
itrztl.  Zts.,  Berlin,  1894,  23:  253. 

Man,  36:  A  dose  of  15  grains  of  antipyrin  was  followed  by  the  appear- 
ance of  an  erythematous  eruption  on  the  back  of  the  hand. 

Bkocq,  L.    Eruption  erythemato-pigmentee  fixe  due  k  I'antipyriue.    Ann.  dermat 
syph.,  Paris,  1S94   (3.  s. ) ,  5 :  308. 

Ingestion  of  antipyrin  was  followed  by  an  eruption  of  dark-red  plaques. 

Du  Castex.    Discussion  of  paper  by  Brocq.  ibid.,  p.  312. 

On  three  occasions  the  patient  suffered  from  erythematous  patches  on 
the  glans  and  left  eyelid  after  taking  antipyrin. 

FouB-MER.  A.     Pseudo-syphilide  palmaire  determinoe  par  I'antipyriue.     Bui.  soc. 
frang.  dermat.  syph.,  Paris,  1894,  5:  175. 

A  dose  of  antipyrin.  from  7.5  to  15  grains,  produced  an  eruption  in  the 
palm  of  the  hand  which  closely  resembled  syphilis. 

Haxlopeau.     Recidive    in    situ    d'un    erytheme    polymorphe.     Bui.    soc.    fraug. 
dermat.  syph.,  Paris,  1894,  5:  481. 

Ingestion  of  7.5  grains  of  antipyrin  was  followed  by  great  restlessness 
and  the  appearance  of  au  erythematous  and  vesicular  eruption. 

Habtzell,  M.  B.     Urticaria  following  the  administration  of  antipyrin.     Arch. 
Pediat.,  New  York,  1894,  11:  371. 

Boy.  2:  Administration  of  0.75  grain  of  antipyrin  was  followed  by  the 
appeai-ance  of  an  eruption.  A  second  dose,  given  experimentally,  produced 
a  similar  result. 

Hood,  .1.  .1.     Toxic  svmptoms  produced  by  antipyrin.     Australas.   Med.   Gaz., 
Sydney,  1894,  13:  150. 

Patient,  a  woman,  had  an  itching  lichen  ruber.  Ingestion  of  10  grains 
of  antipyrin  caused  an  aggravation  (jf  the  symptoms  and  the  appearance  of 
a  general  erythematous  eruption. 

JADA.S.S0HN.     Discussion  of  pai^er  by  Brasch,  1894,  p.  624. 

Man,  70:  A  few  doses  of  antipyrin  caused  the  appearance  of  a  bullous 
eruption  on  the  lips,  bauds,  and  genitals. 

JuLLiEN,  cited  by  Brocq,  1804,  ibid.,  p.  31.3. 

f'as*'  of  antiiiyrin  exaiitliem  like  that  described  by  Brocq. 

MoELLEK,    .1.     Zur    Kenntniss    des    Antipyrin-Exanthems.      Tlierap.    Monatsh.. 
Berlin,  1894,  S:  565.     (See  also  Moeller.  1892.) 

Ingestion  of  7.5  grains  of  antipyrin  was  followed  by  the  development  of 
Hmall  blisters  on  the  hands  and  genitals. 

ScHiFi-.     Arch.  Dermat.  Syph.,  Wien,  1S!M,  27:  315. 

A  papular  erythema  followed  the  administration  of  antipyrin  to  u  child 
10  montha  old. 


58  ACETANILID,   ANTIPYRIN,   AND   PHENACETIN. 

WiCKHAM,  L.  Erytlieme  provoque  par  rantipyrine ;  pseudo-roseole  syphilitique. 
Ann.  dermat.  syph.,  Paris,  1894  (3.  s.),  5:  337. 

The  ingestion  of  0.5  drachm  of  antipyrin  was  followed  by  the  develop- 
ment of  a  roseola  resembling  that  of  syphilis. 

1895. 

Ballin.     Description   d'une  assez  bizarre  eruption  antipyrique.       Lyon  med., 

1895,  80:  388. 

On  a  number  of  occasions  the  ingestion  of  antipyrin  by  the  same  patient 
was  followed  by  an  eruption  of  red  patches  involving  the  greater  part  of 
the  body. 

Batjdouin,  G.    Bui.  soc.  frang.  dermat.  syph.,  Paris.  1895,  6:  121. 

Two  cases  in  which  an  itching  eruption  followed  the  ingestion  of  anti- 
pyrin. 

BoDiN,  L.  Eruptions  bulleuses  emphigoides  dues  a  I'antipyrine.  Presse  med., 
Paris,  1895,  p.  487. 

Case  in  which  an  eruption  followed  the  ingestion  of  15  grains  of  anti- 
pyrin. 

DuBREUiLH,  W.  ifirytheme  fixe  cause  par  I'antipyrine.  Arch.  clin.  Bordeaux 
1895,  4:  383. 

Each  time  the  patient  took  22.5  grains  of  antipyrin  a  red  infiltrated 
patch  appeared  on  the  left  cheek. 

Gastou.     lEruption  d'antipyrine.     Med.  mod.,  Paris,  1895,  6:  271. 

Ingestion  of  15  grains  of  antipyrin  was  followed  by  the  appearance  of 
an  ui'ticarial  eruption  with  thd  formation  of  bullae  and  subsequent  ulcera- 
tion. 

Knight,  E.  Peculiar  susceptibility  to  the  effects  of  antipyrin.  Brit.  Med.  J., 
London,  1895,  1:  1132. 

A  dose  of  10  grains  of  antipyrin  in  one  case  caused  the  appearance  of 
an  urticarial  eruption  and  in  another  violent  sneezing,  swelling  of  the  nose 
and  throat,  and  dyspnea. 

Morel-Lavall£e,  a.  Placards  pigmentes  indelebiles  coixsecutifs  k  un  Erythema 
antipyrine  recidivant  sur  place.  Ann.  dermat.  syph.,  Paris,  1895  (3  s.), 
6:  325. 

The  ingestion  of  15  grains  of  antipyrin  was  followed  by  an  eruption 
resembling  nettle-rash. 

Payne,  W.  H.     Brit.  Med.  J.,  London,  1895,  1:  1132. 

A  case  in  which  10  grains  of  antipyrin  caused  an  urticarial  eruption 
within  fifteen  minutes  after  the  ingestion  of  the  drug. 

RuGE,  H.  ITeber  einen  Fall  von  Idiosynkrasie  gegen  Antipyrin.  Cliarite-Ann., 
Berlin,  1895,  20:  245. 

Woman,  35:  A  dose  of  15  grains  of  antipyrin  was  followed  by  a  rise  in 
temperature  of  4.5°  and  the  appearance  of  an  eruption. 

Russell,  W.  M.  Peculiar  susceptibility  to  the  effects  of  antipyrin.  Brit.  Med. 
J.,  London,  1895,  1:  1019. 

The  ingestion  of  3  grains  of  antipyrin  (which  was  vomited  almost  imme- 
diately) was  followed  by  soreness  of  the  gums  and  the  development  of  an' 
eruption  upon  the  body. 


LITERATURE    ON    ANTIPYRIN    POISONING.  59 

Sedgwick.  W.    Autipyriu  rash.    Brit.  Med.  J.,  Loudon.  1S95,  1 :  58. 

On  two  occasions  the  ingestion  of  10  grains  of  antipyriu  was  followed  by 
the  appearance  of  a  bright  red  rash. 

Suss.     Note  sur  deux  cas  d'erytheuie  phlyctenulaire  produit  par  I'autipyriue. 
France  uied.,  Paris,  1895,  42:  177. 

(1)  The  ingestion  of  45  grains  of  antipyriu  in  divided  doses  was  followed 
by  the  appearance  of  irregular  purplish  spots  upon  the  extremities.  (2) 
Antipyriu  taken  for  headache  caused  the  appearance  of  a  rash  upon  the 
body. 

Talamox.  C.  Eruptions  medicamenteuses.  Med.  mod.,  Paris,  1895,  6:  212. 
(1)  The  ingestion  of  30  grains  of  antipyriu  was  followed  by  the  appear- 
ance of  a  scarlatiuiform  eruptiou.  (2)  The  ingestion  of  antipyriu  was  fol- 
lowed on  the  third  day  by  the  appearance  of  a  morbilliform  rash.  (.3)  Ad- 
ministration of  antipyriu  to  a  typhoid  i)atient  caused  an  eruptiou  which  was 
purpuric  in  character.  (4)  Author  had  seen  a  papular  erythema,  more  or 
less  abundant,  following  the  administration  of  antipyriu  to  tubercular  pa- 
tients iu  five  or  six  instances. 

1896. 

Armaignac.    Mem.  bul.  soc.  med.  chir.  Bordeaux,  189G,  p.  416. 

On  three  occasions,  following  the  ingestion  of  30.  45.  and  60  grains  of 
antipyriu,  respectively,  a  girl  suffered  from  an  eruption  of  small,  slightly 
indurated  papules. 

BRigrET.     A  propos  d'un  cas  exceptionnel   d'intolerance  pour  I'antipyrine.     J. 
med.  chir.  jn-at.,  I'aris,  1896,  67:  929. 

Youth.  24 :  A  severe  pruritus  lasting  two  days  followed  the  ingestion  of 
15  grains  of  antipyriu.  Subsequentlj'  a  similar  affection  followed  the  in- 
gestion of  7.5  grains. 

CouLo.v.   ("II.,   ET  Verny.   G.     Uu  cas  d'intolerance  antipyrinique.     Bull.   med. 
nord,  Lille,  1896,  35:  301. 

Youth,  23,  headache:  Four  hours  after  taking  15  grains  of  antipyriu  an 
eruption  rjf  reddish  spots  ajipeared  u]ton  the  body. 

Descheemakkk.     Nouvel    exemple   d'urlicaire    antipvrinique.     Bul.    m^d.    nord, 
Lille.  1896,  35:  .562. 

Man.  .59:  The  ingestion  of  15  grains  of  anti|tyriu  was  followed  by  the  de- 
velopment of  an  urticarial  eruption  around  the  right  eye,  and  severe  head- 
ache. 

Galew.ski,     Arch.  Derma t.  Syph.,  Wlen.  1896,  34:  105. 

The  ingestion  of  15  grains  of  antipyriu  was  followed  by  an  eruption  upon 
the  skin,  necrotic  i)atches  in  the  mouth  and  throat,  fever,  and  bleeding. 

KUS8,    reported    liv    Dalche.      P.iil.    ni('m.    soc.    nit'd.    hup.    I'ni-is,    ISIK".    CA.    s. ), 
18:  707. 

Man.  '.'A,  headache:  Tlie  ingestion  of  antii)yriii  was  followed  after  leu 
hours  by  an  intense  ilcbiiig  with  redness  at  the  right  ala  of  the  nos*?,  on 
the  right  middle  finger,  and  the  scrotum,  followed  by  the  formation  of 
blisters. 


60  ACETANILID,    ANTIPYKIN^   AND    PHENACETIN. 

Mabtin.     Mem.  et  bul.  soc.  med.  cliir.  Bordeaux,  1896,  p.  416. 

Tlie  ingestion  of  antipyrin  in  2.5  grain  doses  was  followed  by  a  general 
pemphigoid  eruption. 

Spietschka.  Discussion.  Yerliaudl.  deutscli.  dermat.  Gesell.,  1896,  p.  151. 
Wien  and  Leipzig. 

Woman,  34 :  Took  from  15  to  22.5  grain  doses  of  antipyrin  for  years. 
At  present  4.5  grains  produce  urticaria  and  edema  of  the  face. 

Webber,  H.  W.    A  case  of  antipyrin  eruption.     Lancet,  London,  1896,  1:  1562. 
Woman,  53 :  A  morbilliform  eruption  followed  the  ingestion  of  10-grain 
powders  of  antipyrin  twice  daily,  for  three  weeks. 

ISQT'. 

Cl:ement,  V.     Des  accidents  dus  a  I'emploi  de  I'antipj^rine.     Paris,  1897. 

Five  cases  in  which  an  eruption  upon  the  skin  followed  the  administra- 
tion of  antipyrin,  and  one  in  which  ingestion  of  the  drug  was  followed  by 
marked  prostration. 

Deansaet.  De  I'antipyrinisme :  Cas  d'eczema  bulleux  generalise  consecutif 
a  une  faible  dose  d'antipyrine ;  deux  cas  de  contractures  musculaires.  Echo 
mM.  nord,. Lille,  1897,  1:  144. 

(1)  Man,  40:  Two  grains  of  antipyrin  produced  a  general  bullous  eczema, 
lachrymation,  and  the  symptoms  of  coi'yza.  (2)  In  two  cases  the  adminis- 
tration of  7.5  to  15  grains  of  antipyrin  was  followed  by  rapid  contractions 
of  the  muscles  of  the  legs  and  arms. 

DuHOURCAU.     Accidents  dus  a  I'antipyrine.     Med.  mod.,  Paris,  1897,  8:  103. 
.    On  two  occasions  the  ingestion  of  antipyrin  produced  an  erythematous 
eruption  in  the  case  of  a  girl. 

Ehbmann,  S.  Die  lokalisirten  Erytheme  im  Allgemeinen  und  die  lokali- 
sirten  Antipyrinerytheme  im  Besondern.  Wiener  med.  Wochenschr.,  1897, 
47:1697. 

Three  cases  in  which  antipyrin  caused  the  development  of  a  skin  erup- 
tion, in  one  of  which  it  produced  swelling  of  the  right  eyelid  and  itching 
and  enlargement  of  the  papillae  of  the  tongue. 

GoLDscHMiDT,  D.  Cas  d'intolerance  excessive  pour  I'antipyrine.  Bul.  gen. 
therap.   (etc.),  Paris,  1897,  132:  277. 

Young  woman,  headache:  Ingestion  of  a  dose  of  migrainine  was  fol- 
lowed by  itching  of  the  extremities,  lips,  and  eyelids.  On  the  next  day 
there  was  swelling  of  the  affected  parts  and  on  the  third  day  blisters  ap- 
peared upon  the  hands  and  feet. 

Htjber,  A.  Nebenwirkungen  von  Arzneimitteln.  Cor.-Bl.  f.  schweiz.  Aerzte, 
1897,  27:  737. 

The  ingestion  of  migrainine  in  15-grain  doses  was  followed  by  severe 
cutaneous  symptoms  and  ulceration  with  the  formation  of  pseudo-mem- 
branes in  the  mouth. 

Leeoux,  C.  Purpura  generalise,  stomatite  pemphygoi'de  hemorrhagique, 
troubles  trophiques  des  ongles  consecutifs  a  I'ingestion  d'un  gramme  d'an- 
tipyrine.    J.  Clin,  therap.  inf.,  Paris,  1897,  p.  606. 

Woman,  32 :  A  general  pemphygoid  eruption  with  the  formation  of  blis- 
ters in  the  mouth  and  trophic  disturbances  of  the  nails  followed  the  use  of 
antipyrin. 


LITERATURE    ON    ANTIPYRIN    POISONING.  61 

MiBELLi.  V.     Su  gli  eritemi  fissi  da  antipirina.     Gior.  ital.  mal.  ven.,  Milano, 
1897.  32:  575. 

RuYSSEN.  C.     Erythenie  rubeoliforme  cUl  k  I'antipyrine.     Echo  med.  nord,  Lille, 
1897,  1 :  359. 

Girl.  2.3.  tuberculosis:  A  single  dose  of  15  grains  of  antipyrln  daily  caused 
the  appearance  of  a  morbilliform  rash. 

ToNNEL  ET  Raviart.     Erythemes  bulleux  dus  a   Tingestion  d'antipyrine;   leur 
pathogenie.     Echo  med.  nord,  Lille,  1897.  1:  18. 

Woman,  57 :  The  ingestion  of  15  grains  of  antipyrin  was  followed  on 
three  occasions  by  a  bullous  eruption. 

ViDAL.  A.     Intolerance  exceptionnelle  pour  I'antinyrine.     Gaz.  hebd.   sci.  med 
Bordeaux.  1897,  18:  51. 

An  eruption  of  red  edematous  patches  followed  the  ingestion  of  between 
15  and  30  grains  of  antipyrin. 

1S9S. 

Apolant.  H.     Die  Antipyrinexantheme.     Arch.  Dermat.  Syph.,  Wien  and  Leip- 
zig, 1898,  46:  364. 

The  author  took  15  grain.s  of  antipyrin  for  headache.  After  ten  minutes 
there  appeared  erythema,  edema  of  the  eyelids,  and  itching  of  the  genitals. 
The  .symptoms  recurred  when  the  dose  was  repeated. 

Blaschko.     See  Lesser,  1898. 

Five  cases  in  which  the  ill  effects  following  the  ingestion  of  antipyrin 
were  exhibited  by  the  skin  or  mucous  membranes. 

Bbongniakt,  G.     Sur  un  cas  de  roseole  m^dicamenteuse  due  k  Tantipyrine  prise 
par  la  voie  gastrique.     Echo  med.  nord.  Lille,  1898,  2:  404. 

A  dose  of  15  grains  of  antipyrin  daily  caused  the  appearance  of  a 
morbilliform  eruption  on  the  eighth  day. 

Bruck.     See  Lesser,  1898. 

A  patch  the  size  of  a  half  dollar  appeared  on  the  right  side  of  the 
abdomen  each  time  the  patient  took  antipyrin. 

Gebebt.     See  Lesser,  1898. 

Two  cases  in  which  herpes  progenitalis  followed  the  ingestion  of  an- 
tij)yrin. 

LE.SSEB,     Ueber  Antipyrin-Exantheme.     Dermat.  Zts.,  Berlin.  1898,  5:  243. 

Two  cases  in  which  the  use  of  juitipyriii  was  followed  by  skin  symptoms. 
In  one  they  consisted  of  erythematous  i»apules,  and  in  the  other  of  an  oval 
brown  spf)(   on   the  abdomen. 

SiBLT,  L.     Eruption  antipyrinique.     Bui.  soc.  franc,  dermat.  sy{)h.,  Paris,  1898, 
0:  188. 

Antipyrin  In  15-grain  drtses  cau.sed  the  ar>p»'arance  of  an  erui)tion  upon 
the  skin. 

\VKCii8Er.MAN.N,   W.      I'eber   .VnlipyriiicxiiMdiem.      IxmiIscIk"   med.   Woohenschr., 
lA'ipzig  and   Berlin,   1898,  24:  .335. 

Five  caseH  In  which  lli<!  Ingestion  <>f  anlipyn'M  w;is  followi-d  iiy  mani- 
festations on  the  part  of  the  skin. 


62  ACETANILID,    ANTIPYRIN,    AND    PHENACETIN. 

1899. 

D'AuLNAY,  G.  R.     Intoxication  par  la  migraiuine.     Bui.  gen.  de  therap.    [etc.] 
Paris,  1899,  137:  857. 

The  ingestion  of  7.5  grains  of  migrainine  was  followed  by  pain  in  the 
stomach,  urticaria,  diarrhea  with  tenesmus,  burning  on  micturition,  rapid 
pulse,  and  accelerated  respiration. 

X901. 

Troisfontaines,    p.      Eruption    pemphigoTde    antipyrinique.      Belgique    mM., 
Gand.  Haarlem,  1901,  8   (2)  :  1. 

Man,  38,  headache:  Two  1.5-grain  doses  of  antipyrin  with  a  two-hour 
interval  were  followed  by  vomiting  and  diarrhea,  and  the  appearance  of 
an  itching  scarlatiniform  eruption. 

190S. 

Bernard,  J.     i*ccidents  consecutifs  a  I'absorption  d'antipyrine.     Gaz.  med.  Pi- 
cardie,  Amiens,  1902,  20:  407. 

A  nervous  patient,  35  years  of  age,  took  10  grains  of  antipyrin  and  3.75 
grains  of  hydrobromate  of  quinine.  Purpuric  spots  appeared  upon  the 
palm,  sole,  and  fingers,  followed  by  desquamation.  There  was  also  redness 
of  the  urethra  and  glans,  with  discharge. 

Cardoso,  A.     Um  casa  de  idiosyncrasia  para  a  antipyrina.     Med.  mod.,  Porto, 
1902,  9:  250. 

Crouzel,  E.     Sur  un  case  d'idiosyncrasie.     J.  med.  Bordeaux,  1902,  32:  794. 

Every  time  that  the  author  took  antipyrin,  3.75  grains,  there  appeared 
on  the  dorsum  of  the  left  hand  a  red  erythematous  patch,  painful  on 
pressure. 

1903. 

Claverie.       Eruption,     erythemato-bulleuse     due     a     I'antipyrine.     Rev.     m§d. 
I'Afrique  du  nord,  Alger,  1903,  6 :  2228. 

Man.  72,  headache :  Six  hours  after  the  ingestion  of  15  grains  of  anti- 
pyrin erythematous  spots  appeared  all  over  the  body,  with  the  subsequent 
development  of  vesicles  and  bullae. 

Danlos.     Eruption  a  type  d'erytheme  polymorphe  produite  par   I'antipyrine. 
Bui.  soc.  frang.  dermat.  syph.,  Paris,  1903,  14:  233. 

On  two  occasions  the  ingestion  of  antipyrin  was  followed  by  nervousness, 
insomnia,  a  skin  eruption,  and  the  development  of  blisters  in  the  mouth 
and  upon  the  genitals. 

Dariek.     Antipyrinides.     Rev.  internat.  med.  chir.,  Paris,  1903,  14:  362. 

A  bullous  eruption  upon  the  dorsum  of  the  hands,  and  vesicles  upou  the 
auricle  and  knee  followed  the  use  of  antipyrin. 

Nagatomi,    J.     (Antipyrin    exanthemata.)     Chingai    Iji    Shinpo,    Tokio,    1903, 
p.  515. 

Roux.     Un   cas   d'intoxication   par    I'antipyrine.     Poitou    med.,    Poitiers,    1903, 
18:  18. 

Woman,  54,  headache :  Two  7.5-grain  powders  of  antipyrin  were  followed 
by  dyspnea,  and  great  redness  and  swelling  of  the  skin  of  the  face  and  body. 

Shishido,    S.     (Antipyrin    exanthemata.)     Chingai    Iji    Shinpo,    Tokio,    1903. 
p.  217. 


LITERATURE    ON    AXTIPYRIN    POISONING.  63 

1904. 

Behaegei..     Erytheme  pigmente  fixe  dfl  a  I'antipj-riue.     J.  med.  Bruxelles,  1904, 
9:  420. 

An  eruption  of  reddish-brown  spots  followed  each  dose  of  22.5  grains  of 
antipyrin. 

Di'bois-Havenith.     Erytheme  pigmente   flxe   dfl   a    I'administration   de   I'anti- 
pyrine.     Presse  med.  beige,  Bruxelles,  1904,  56:  731. 

An  erythematous  eruption  followed  the  ingestion  of  22.5  grains  of  auti- 
pyrin. 

LowY.  K.     I'eber  zwei   Falle  von  Autipvrin-Exanthem.     Arch.   Dermat.   Syph., 
Wien,  1904,  68:  167. 

(1)  The  ingestion  of  a  teaspoonful  of  headache  powder  was  followed  by 
general  pruritus,  an  eruption  upon  the  skin,  and  marked  depression.  (2)  A 
dose  of  15  grains  of  antipyrin  was  followed  by  a  morbilliform  eruption  and 
great  swelling  of  the  face. 

Malherbe,  H.     Verge  noire  par  eruption  antipyrinique.     J.  mal.  cutan.  syph., 
Paris.  1904,  16:  499. 

The  ingestion  of  22.5  grains  of  antipyrin  was  followed  by  an  almost  black 
discoloration  of  the  genital  organs,  which  was  slow  in  disappearing. 

1905. 

Bruning.     Zur    Pathogenese    der    Antipyrinexantheme.     Charite-Ann.,    Berlin, 
190.5,  29:  787. 

Each  time  the  patient  took  antipyrin  he  suffered  from  ulceration  of  the 
mucous  membrane  of  the  mouth  and  a  vesicular  eruption  upon  the  body, 
including  the  genital  organs. 

Yamada,    K.      Noch    einmal    fiber    die    Antipyrinexanthema.      (Ausz.,    fac.    4.) 
Hifubyog.       Kiu  Hiniokibyog.     Zasshi,  Tokyo,  1905,  5:  423. 

1906. 

Degle,  II.     Eiiie  eigentiimliche  Form  einer  toxischen  Dermatose  nach  Antipy- 
ringebrauch.     Wien.  med.  Presse,  1906,  47:  21.54. 

The  ingestion  of  15  grains  of  antipyrhi  twice  daily  was  followed  by  the 
appearance  of  an  eruption  resembling  miliaria  riii)ra. 

1007. 

(iiLLES.     Intoxication  par  rantipyrine  choz  une  accouchee.     Toulouse  med.,  1!M»7 
(2  .s.),  9:  26. 

A  doso  of  7.5  grains  of  antipyrin  was  followc'd  by  tlie  ajtpearance  of  an 
erytliematous  eruption.  f)n  the  next  day  there  was  edema  of  the  lower 
extremities  and  profuse  dijirrhcM. 

(A.SKS   OK   fOLLAPSK. 

In    tlif!   following:   instances  collapse   formod   the  mo.st  prominent 

.     feature   of   the   clinical   history.     The   symptoms   e.xhihiled   were    in 

most  cases  the  usual  ones  of  pallor  of  the  skin,  coldness  of  (he  ex- 

treniilies.  <■()](]   ptrspiration.  rapid  and   f('el)le  pulse,  and  an  anxious 

and  jiinchcd  (!\{jre>sion,  the  severity  of  the  symptoms  depending  on 


64  ACETAlSriLID,    ANTIPYRIN,    AND    PHENACETIN. 

the  intensity  of  the  poisoning.  In  many  of  the  cases  the  skin,  diges- 
tive tract,  or  other  parts  of  the  body  presented  abnormal  symptoms 
in  addition  to  those  of  collapse.  Cyanosis,  however,  appeared  in  only 
a  very  few  instances. 

1884. 

HucHAED.    Nouveaux  faits  relatifs  a  Taction  pbysiologique  et  therapeutique  de 
I'antipyrine.     Bui.  mem.  soc.  therap.,  Paris,  1884   (2  s.),  11:205. 

Child,  7,  typhoid:  Collapse  followed  the  ingestion  of  12  grains  of  anti- 
pyrin.    The  case  resembled  one  of  carbolic-acid  poisoning. 

Israel,  E.     Om  Antipyrinet.     Hosp.-Tid.,  Kjobenhavn,  1884  (3  s.),  2:  1129. 
Boy,  13,  typhoid :  Collapse  followed  the  ingestion  of  antipyrin. 

May,  F.     Antipyrin,  das  neueste  Antipyreticnm.     Deutsche  med.  Wochenschr, 
1884,  10:  390. 

Man,  25,  pneumonia :  One-half  drachm  of  antipyrin  at  7  and  8  p.  m.,  and 
15  grains  at  9  p.  m.  were  followed  by  severe  collapse. 

1885. 

Blore.     Death  after  the  use  of  antipyrin;  necropsy.     Lancet,  London,  1885,  1: 
882. 

Woman,  35:  At  3  p.  m.,  her  temperature  being  103°  and  pulse  132  and 
feeble,  she  was  given  35  grains  of  antipyrin,  and  three  hours  later  one- 
half  of  this  quantity.  By  11  p.  m.  her  temperature  was  normal.  She 
passed  a  restless  night,  with  diarrhea  and  vomiting,  fell  into  a  condition 
of  collapse,  and  died  thirty-two  hours  after  taking  the  antipyrin. 

BoLDT,  see  Draper,  W.  H.    Med.  Bee,  New  York,  1885,  27 :  414. 

In  2  cases  of  puerperal  septicemia  the  ingestion  of  1  drachm  of  anti- 
pyrin was  followed  by  prostration  and  semicoma.  The  symptoms  resem- 
bled those  of  carbolic-acid  poisoning. 

CossMANN.     Collaps  nach  Antipyrin.     Prakt.  Arzt,  Wetzlar,  1885,  26:  106. 

Girl,  19,  typhoid :  Collapse  followed  the  ingestion  of  1  drachm  of  anti- 
pyrin in  2  doses,  with  a  two-hour  interval. 

Favre,    C.     De   I'antipyrine    dans   la    fievre   hectique    des    tuberculeux.     Lyon, 

1885. 

Pulmonary  tuberculosis.  A  dose  of  22.5  grains  of  antipyrin  was  followed 
by  nausea,  chills,  and  coldness  of  the  lower  extremities.  Later,  a  drachm 
administered  within  five  hours  produced  a  tendency  to  collapse. 

GoTZE.      Einige  Bemerkungen   fiber   die   Wirkung   des   Antipyrin.     Berl.    klin. 
Wochenschr.,  1885,  22:  145. 

(1)  Five  hours  after  taking  1.25  drachms  of  antipyrin  in  3  doses  the 
temperature  fell  to  96.6°,  with  cyanosis  and  symptoms  of  collapse.  A 
similar  result  followed  the  ingestion  of  1  drachm,  and  later  0.75  of  a 
drachm.  (2)  Boy,  14:  The  ingestion  of  37.5  grains  of  antipyrin  in  3  doses 
was  followed  by  symptoms  of  collapse  and  a  fall  in  the  temperature  of  9°. 

HuMBERT-MoLLiERE.     Discussion  of  paper  by  RoUet.     Lyon  med.  1885,  49:  472. 
Collapse  followed  the  ingestion  of  antipyrin  in  the  case  of  an  old  tuber- 
culous woman. 


LITERATURE    ON    ANTIPYRIIv    POISONING.  65 

Jaccoud.  Sur  les  efl'ets  antitberuiiqiies  de  l;i  tlialliue.  P>ul.  acad.  ined.,  Paris, 
1SS5   (2.  s.),   14:  1443. 

Phthisis:  (1)  lugestiou  of  0.5  drachm  of  aiitipyrin  daily  caused,  on  the 
third  day.  a  fall  of  9°  in  the  i>atieut's  teniiterature  within  three  hours. 
(2)  Serious  collai»se  followed  the  ingestion  of  7.5  grains. 

Mason,  A.  L.  Typhoid  fever  at  the  Boston  city  hospital  in  18S4-18S5;  with 
remarks  on  the  use  of  antipvrine.  Boston  Med.  and  Surg.  J.,  18S5,  113: 
535. 

Out  of  KKt  typhoid-fever  patients  treated  with  antipyrin,  6  showed 
symptoms  of  collapse  within  an  hour  after  the  ingestion  of  20  or  30  grains 
of  the  drug. 

ScHtJLLER.   <;.     Collaps  nach  Antipyrin.     Prakt.   Arzt,   Wetzlar,   1885,   26:  145. 
Youth,  21.   typhoid:  Severe  collapse  followed  the  use  of  antipyrin. 

ScHULZ,  li.  Rehandlung  des  Typhus  abdominalis  mit  Antipyrin.  Deutsche 
med.  Wochen.schr.,  Berlin,  1885,  11 :  333. 

The  ingestion  of  1  drachm  of  antipyrin  in  2  doses  was  followed  by  symp- 
toms of  collapse. 

Stbauss.     Zur  Wirkuug  des  Antipyrius.     Berl.  klin.  Wochenschr.,  1885,  22:  5G2. 
Typhoid :  The  ingestion  of  1.25  drachms  of  antipyrin  in  3  doses  was  fol- 
lowed by  collapse. 

1886. 

SucHARi).  Soc.  vaudoise  de  med.,  Oct.  10,  1885,  Rev.  med.  de  la  Suisse  rom., 
Geneve,  1886,  6:56. 

Phthisis:  Collapse,  followed  by  death,  resulted  from  the  ingestion  of 
about  12  grains  of  antipyrin  during  the  night. 

BuNGEBOTii.  Beobachtungen  iiber  das  Antipyrin  bei  infecticisen  Erkrankun- 
geu  der  Kinder.     Charite-Ann.,  Berlin,  1886,  11:599. 

(1)  In  22  cases  of  typhoid  fever  in  children  mild  collapse  followed  the 
administration  of  antii)yrin  in  3  cases;  severe  collapse  in  3  cases;  dan- 
gerous cardiac  weakness  in  2  cases;  and  a  rubeola-like  eruption  in  1  case. 

I>EMi£:viLLK.  Soc.  vaudoise  de  med.,  Oct.  10,  1885.  Kev.  med.  de  la  Suisse 
rom.,   Geneve,   1886,   (>:  56. 

Serious  collapse,  with  coma  lasting  three  days,  followed  the  ingestion  of 
45  grains  ctf  antipyrin  in  2  doses  within  two  hours. 

Gkaham,  VV'.  Unpleasant  effects  of  antipyrin.  Canada  Lancet,  Toronto,  1885- 
1886,  18:  138. 

Twelve  grains  of  antipyrin  taken  every  three  luairs  produced  severe  col- 
lapse and  an  eruption  of  purpuric  macuhe  upon  tlic  back. 

PosAiJSKY,  S.  Antifiyrin  bei  crupiiser  Pneumonic  I  »ciitsclie  nicd.  Woclieiiscbr., 
Berlin,  1886,  12":  636. 

Lobar  pneumonia  :  In  5  cases  out  of  25  collapse  followed  the  ingestion  <»f 
a  few  doses  of  antipyrin.    In  2  cases  there  was  also  an  erythema. 

Rkiiii.kn,  M.  Ueber  Antipyrin.  Deutsches  Arcli.  kiln.  .Med.,  Leipzig,  l,s,s5-(5, 
:JS:  5;i4. 

Two  cases  of  collapse  in  89  cases  treated  witli  antii»yriii;  1  in  tubercular 
meningitis,  the  other  in  gangrene  of  the  luug. 

82:il9— P.ull.  \2(i—ir.t 5 


66  ACETANILID,    AFTIPYEIN,    AND    PHENACETIN, 

Welch,  W.  M.    Clinical  note  on  the  use  of  antipyrin,    Med.  News,  Philadelphia, 

1886,  48 :  10. 

A  single  dose  of  10  grains  of  antipyrin  administered  in  typhoid  fever 
produced  symptoms  of  collapse. 

1887. 

Bebnotjlli,  D.     Zur  Kenntniss  der  Nebenwirkungen  des  Antipyrin.     Cor.-Bl.  f. 
schweiz.  Aerzte,  Basel,  1887,  17:  357. 

Woman,  52,  rheumatism :  A  dose  of  15  grains  of  antipyrin  was  followed 
by  mild  collapse  and  vomiting.  A  month  later  a  similar  dose  produced 
vomiting,  cyanosis  of  lips,  dyspnea,  and  a  scarlatiniform  eruption. 

Bbooks,  L.  J.    Clinical  value  of  antipyretics.    Med.  Times,  Philadelphia,  1886-87, 
17:  794. 

(1)  Boy,  9:  The  ingestion  of  10  grains  of  antipyrin  was  followed  by 
cyanosis  and  symptoms  of  collapse.  (2)  Symptoms  of  collapse  followed  the 
ingestion  of  two  10-grain  doses  of  the  drug.  (3)  A  morbilliform  eruption 
appeared  after  the  use  of  antipyrin. 

Cheron,   p.     Contribution  a   I'etude  du   danger   de  I'antipyrine.     Union   med., 
Paris,  1887  (3.  s.),  43:  907. 

Typhoid :  Collapse  followed  the  ingestion  of  15  grains  of  antipyrin  in 
two  doses  with  an  interval  of  five  hours. 

Hays,  G.  D.     A  caution  as  to  the  use  of  antipyrin.     New  York  Med.  J.,  1887, 
45:  100. 

Three  cases  of  collapse  following  the  ingestion  of  antipyrin.  One  was 
a  case  of  acute  rheumatism,  and  the  other  two  of  typhoid  fever. 

Henderson,  R.  B.     Two  cases  of  poisoning  from  antipyrine  and  nux  vomica. 
Med.  Rec,  New  York,  1887,  31 :  95. 

Report  of  two  cases  of  poisoning,  in  which  both  antipyrin  and  nux  vomica 
were  administered.  Both  were  characterized  by  prostration,  and  in  one 
death  resulted. 

Note  on  collapse  following  antipyrin.     Indian  Med.  J.,  Lahore,  1887    (n.  s.), 
1 :  273. 

The  ingestion  of  10  grains  of  antipyrin  by  a  soldier  to  reduce  temperature 
was  followed  by  cyanosis  and  collapse. 

Jacoby,  G.  W.     Med.  Rec,  New  York,  1887,  32 :  581. 

Author  had  seen  collapse  follow  a  dose  of  20  grains  of  antipyrin. 

LuTAUD.     Contribution  a  I'etude  des  dangers  de  I'antipyrine.     J.  med.,  Paris, 

1887,  12:  825. 

The  ingestion  of  15  grains  of  antipyrin  in  two  doses,  with  a  three-hour 
interval,  was  followed  by  collapse. 

Mendel.     Die    Anwendung    des    Antipyrin     bel     Nervenkrankheiten.     Therap. 
Monatsh.,  Berlin,  1887,  1:  259. 

Author  had  observed  collapse  following  the  ingestion  of  antipyrin  in 
two  cases. 

Weill,  E.,  and  Chabannes.     Observation  de  fievre  typhoi'de  traitee  par  I'anti- 
pyrine et  terminee  par  la  mort.    Lyon  med.,  1887,  56:  426. 

Typhoid:  The  ingestion  of  9.5  drachms  of  antipyrin  was  followed  by 
a  relapse,  during  which  the  patient  received  6.25  drachms  in  seven  days. 
This  was  followed  by  collapse  and  death. 


LITERATURE    ON    ANTIPYRIN    POISONING.  67 

Wilson.  J.  C.     Note  on  antipyrin  in  the  treatment  of  sciatica.     Med.  Times, 
Philadelphia,  1SS7-SS,  18:  4S.    . 

Alarming  prostration  followed  the  administration  of  5  grains  of  anti- 
pyrin to  a  very  fat  woman  with  weak  heart  walls. 

188S. 

BiNET.  P.     Soc.  med.  de  Geneve.     5  Sept.,  ISSS.     Rev.  med.  de  la  Suisse  rom., 
Geneve,  1SS8,  8:  635. 

Author  cites  a  case  in  which  a  dose  of  7.5  grains  of  antipyrin  was  fol- 
lowed hy  swelling  of  the  eyelids,  an  itching  eruption,  nausea,  vertigo,  pre- 
cordial pain,  and  loss  of  consciousness. 

D'EsPiNE,  cited  by  Cordet  in  discussion  of  paper  on  "  Des  accidents  produits  par 
I'antipyriue."     Rev.  gen.  cliu.  therap.,  Paris,  ISSS,  2:  709. 

Author  states  that  he  had  seen  collapse  in  children  with  pneumonia 
follow  the  ingestion  of  even  small  doses  of  antipyrin. 

Drasche.     Ueber  die  Nebenwirkungen  des  Antipyrins.     Wien.  klin.     Wochen- 
schr.,  ISSS,  1 :  571. 

Typhoid:  An  enema  containing  0.5  drachm  of  antipyrin  was  followed  by 
a  copious  hemorrhagic  exanthem  and  collapse,  which  ended  fatally. 

Hafftek,  E.     Cor.-Bl.  f.  schweiz.  Aertze,  Basel,  18SS,  18:  743. 

Man,  Go,  pneumonia  :  Fatal  collapse  occurred  one  hour  after  the  inges- 
tion of  15  grains  of  antipyrin. 

MoLLiERE,  H.,  cited  by  Peter  in  "  Les  traitements  de  typhoTdiques."     Bui.  med., 
Paris,  ISSS,  2:  551. 

(1)  Typhoid  patient.  52  years  of  age,  after  taking  antipyrin  for  fifteen 
days,  died  of  cachectic  purpurea  and  debility  induced  by  the  drug.  (2)  In- 
gestion of  antipyrin  by  a  typhoid-fever  patient  2()  years  old  caused  uremic 
convulsions,  which  ended  fatally. 

LoEBL,  .J.  M.     Erfahrungen  iiber  Antipyrin.     Wien.  med.  Presse,  1S8S,  29:  121. 
Child,  6,  typhoid :  Ingestion  of  four  doses  of  antipyrin,  3.25  grains  each, 
was  followed  by  cyanosis  and  symptoms  of  collapse. 

MtJLLER,     II.     Ueber     toxische     Nebenwirkungen     des     Antipyrin.     Cnr.-BI.     f. 
Schweiz.  Aerzte,  Basel,  188S,  18:  OSl. 

Girl,  10,  acute  articuhxr  rheumatism :  Each  dose  of  11  grains  of  anti- 
pyrin was  followed  by  nausea,  dizziness,  itching,  and  a  tendency  to  col- 
lapse. 

Payne.     Discussion  of  paper  by  R.  H.  Lewis.     North  Carolina  Med.  J.,  Wil- 
mington, ISSS,  21:  297. 

Ingestion  of  8  grains  of  antipyrin  was  followed  by  collapse. 

Rapin,  E.     Accidents  dus  tl  rantii)yrine.     Rev.  med.  de  la  Suisse  rom.,  Gen&ve, 
1888,  8:  687. 

Woman,  28,  sciatica  :  Tlie  ingestion  of  1-grain  doses  of  antli»yriii  for  six 
days  was  followed  by  cyanosis,  symptoms  of  collapse,  and  the  appearance 
of  an  Itching  eruption. 

Rousseau.      Des   accidents  causes   par    I'antipyrine.      Rev.   g^n.    clin.    llicrap., 
Paris,  1888,  2:  515. 

The  ingestion  of  7.5  grains  of  aiidpyrin  was  fnllowed  by  itching  of  tlie 
facr*,  swelling  of  the  eyelids,  and  synijitonis  of  collapse.'. 


68  ACETANILID,    AlS'TIPYKIX,    AND    PHENACETIN. 

Sykes.     Discussion  of  paper  by  E.  H.  Lewis.     North  Carolina  Med.  J.,   Wil- 
mington, 1S8S.  21:  2.97. 

(1)  Two  doses  of  10  grains  each  of  antipyrin  caused  collapse  and  death 
in  a  girl  of  10.     (2)   Typhoid  :  Ten  grains  of  antipyrin  caused  coma  and 

collapse. 

1©89. 

Crombie,  a.     The  comparative  value  of  antipyrin.  antifebriu,  and  phenacetin  as 
antipyretics.     Practitioner,  London,  18S9,  43:  270. 

A  case  in  which  collapse  followed  the  ingestion  of  antipyrin. 

V.     KoGERER.       Antipvrinbehandlung     des     hektischen     Fiebers.     Wieu.     klin. 
Wochenschr.,  1SS9,  2:  778;  802. 

Out  of  100  cases  of  phthisis  in  which  antipyrin  was  given,  erythema  was 
noted  in  2  instances  and  collapse  in  1.  The  administration  of  antipyrin  to 
the  same  patient  on  two  occasions  was  followed  by  collapse. 

PuRDON,  C.  S.     Intolerance  of  antipyrin.     Brit.  Med.  J.,  Loudon,  1889,  1 :  1345. 
Man,  50,  sciatica  :  A  5-grain  dose  of  antipyrin  was  followed  by  severe 
nervous  symptoms,  cyanosis,  and  collapse. 

WiNGEAVE,  T.     Ill  effects  of  antipyrin.     Lancet,  London,  1889,  2:  313. 

Woman,  21 :  A  dose  of  10  grains  of  antipyrin  was  followed  by  dyspnea, 

loss  of  power  on  the  left  side,  the  appearance  of  an  eruption,  and  symptoms 

of  collapse. 

1890. 

ScHWABE.     Fall  von  akuter  Antipyrinvergiftung.     Deutsche  Mecl.-Ztg.,  Berlin, 
1890,  11:  501. 

Woman,  22,  neuralgia  :  A  dose  of  15  grains  of  antipyrin  was  followed 
by  dyspnea,  complete  blindness  lasting  thirty  minutes,  and  symptoms  of 
collapse. 

Spitzer,    F.     Selbstmordversuch   mit  Antipvrin.     C'entrbl.    ges.   Therap.,   Wien, 
1890,  8:  134. 

The  ingestion  of  2  drachms  of  antipyrin  within  an  hour  was  followed  by 
swelling  of  the  face  and  eyelids  and  symptoms  of  collapse. 

1S91. 

Watkjns.  Pl.  L.    A  case  of  antipyrine  poisoning.     New  York  Med.  J.,  1891,  51: 
314. 

Woman,  30 :  A  dose  of  about  20  grains  of  antipyrin  was  followed  l)y 
symptoms  of  cyanosis,  collapse,  and  an  eruption  of  white  blotches.  Tlie 
after  effects  lasted  two  months,  during  which  time  she  suffered  from  weak- 
ness, palpitation  of  the  heart,  and  an  occasional  reappearance  of  the 
eruption. 

1S9S. 

GuTTMANN,  p.    TJeber  einen  Fall  von  Antii)vrin-Vergiftung.     Therap.  Monatsh., 
Berlin,  1892,  6:  .560. 

The  ingestion  of  2.5  drachms  of  antipyrin,  in  15  doses,  twice  daily,  was 
followed  by  transient  blindness,  the  appearance  of  an  eruption,  and  symp- 
toms of  collapse. 

1S93. 

Krysinski,    St.      Przypadek   otrucia    antvpiryna.      Gaz.    lek.,    Warszawa,    1893 
(2  s.),  13:  10.31.     (Abs.  Sajous,  1895,  5:  A-3.3.) 

Girl,  20 :  Ingestion  of  81  grains  of  antipyrin  was  followed  by  symptoms 
of  collapse. 


LITERATURE    ON    ANTIPYRIN    POISONING.  69 

Paterson,  D.  R.    The  untoward  effects  of  autipyrin,  ac-etanilide,  and  phenacetin. 
Practitioner,  London,  1893,  51:  241. 

Several  cases  of  antipyrin  poisoning  in  which  the  symptoms  were  mainly 
those  of  cyanosis  and  collapse. 

TuRNBULL,  L.  A.     Case  of  collapse  caused  by  antipyrin.     Meuiphis  Med.  Month., 
1893,  13:  313. 

(1)  Man,  52,  acute  articular  rheumatism:  After  the  second  dose  of  10 
grains  of  antipyrin  the  patient  became  unconscious  and  passed  into  a 
state  of  collapse.  (2)  Woman:  A  dose  of  10  grains  of  antipj'rin  was  fol- 
lowed by  symptoms  of  collapse. 

Melville,  S.     Domestic  drugging;  a  case  of  antipyrin  ])oisoning.     Lancet,  Lon- 
don, 1894,  2:  1515. 

Ingestion  of  30  grains  of  antipyrin  within  a  few  hours  l)y  a  young  woman 
was  followed  by  collapse. 

1800. 

Hayes,  H.  W.  McC.     A  case  of  poisoning  by  antipyrin.     P.rit.  Med.  ,1.,  London, 

1896,  1:  209. 

Following  the  ingestion  of  10  grains  of  antipyrin.  the  patient  became 
cyanosed  and  passed  into  a  condition  of  collapse. 

1S07. 

p]iSENMANN,  A.     Ein  Fail  von  Antipyrinvergiftung.     Tlierai).  Monatsh.,  Berlin, 

1897,  II:  233. 

•Youth,  20,  headache:  Ingestion  of  7.5  grains  of  antipyrin  was  followed  by 
dyspnea,  a  scarlatiniforni  eruiition,  cyanosis,  and  symptoms  of  collapse. 

Newton.  I>.  O.     Notes  on  (wo  cases  of  poisoning  from  antii)yrin.     Quart.  Med. 
J.,  Sheffield,  1897-98,  0:  133. 

(1)  Man,  32:  Took  10  grains  of  antipyrin  for  headache.  Within  two 
minutes  he  was  seized  with  alarming  symptoms— a  feeling  of  suffocation, 
swelling  of  the  face  so  that  the  eyes  were  closed,  lachrymation,  and  dyspnea. 
The  tongue  was  much  swollen  and  the  speech  thick.  There  was  no  eruption. 
He  was  at  work  the  next  day  with  a  slight  swelling  of  the  face.  He  had 
l)reviously  suffered  from  a  similar  attack,  probably  caused,  as  in  this 
instance,  by  antipyrin.  (2)  Woman,  54:  Ten  grains  of  antipyrin  caused 
temporary  blindness,  unconsciousness,  convulsions,  and  synii)toms  of  col- 
lapse. 

CASKS   OF    I'HOSTHATION. 

Under  this  heading  are  grouped  the  cases  in  which  the  systemic 
depre.ssion  was  very  marked,  but  the  symptoms  were  hardly  severe 
enough  to  warrant  classifying  them  under  the  term  "  collapse." 

1884. 

TiLMAN,  O.     Antipyrin  das  neucsle  Antii»yreticuni.     I'.erlin,   1884. 

In  two  cases,  one  of  j)hthisis  and  the  otlier  of  ty|)hoid  fever,  (lie  adminis- 
tration of  antipyrin  was  followed  by  symptoms  of  marked  depression. 


70  ACETANILID,   ANTIPYRIN,   AND   PHENACETIN. 

18S5. 

Baeie,  E.  Note  sur  la  valeur  comparative  de  Tantipyrine  et  du  sulfate  de 
quinine,  dans  le  traitement  de  la  fievre  typhoide.  France  med.,  Paris,  1885, 
2:  1727. 

Two  cases  of  typhoid  fever  in  vphich  the  administration  of  antipyrin  was 
followed  by  mild  symptoms  of  collapse. 

Fedeli,  C.  Di  alcuni  fenomeni  susseguiti  all'  uso  dell'antipirina  in  un  caso  di 
febbre  etica.     Raccoglitore  Med.,  Forli,  1885  (s.  4),  24:  414. 

Following  the  ingestion  of  antipyrin  the  patient's  temperature  rose  to 
106.6°,  accompanied  by  chills  and  syncope. 

1886. 

Johnson,  R.  Clinical  observations  on  the  action  of  antipyrin  and  thallin. 
Lancet,  London,  1886,  2:  388. 

(1)  Phthisis:  Marked  prostration  followed  the  ingestion  of  antipyrin  in 
three  doses  of  10,  20,  and  20  grains,  respectively.  (2)  Three  15-grain 
doses  at  intervals  of  one  hour  caused  similar  symptoms  in  a  boy,  with 
the  addition  of  a  scarlatiniform  eruption. 

issr. 

GuTTMANN,  P.  Zwei  Beobachtungen  liber  Nebenwirkungen  des  Antipyrin. 
Therap.  Monatsh.  Berlin,  1887,  1:  214. 

Report  of  two  cases  of  antipyrin  poisoning,  one  characterized  by  cyanosis 
and  marked  prostration,  and  the  other  by  an  itching  eruption. 

Seifert,  O.  Ueber  Antipyrin  als  Nervinum.  Centrbl.  kliu.  Med.,  Leipzig, 
1887,  8:  649. 

(1)  Ingestion  of  15  grains  of  antipyrin  was  followed  by  pains  in  the 
extremities,  dizziness,  and  headache.  (2)  A  dose  of  15  grains  of  antipyrin 
given  at  7  p.  m.  was  followed  by  a  severe  buzzing  in  the  ears,  which 
prevented  sleep  for  several  hours. 

Weie,  a.  H.     Dangers  of  antipyrin.     Med.  News,  Philadelphia,  1887,  51 :  166. 

A  dose  of  7  grains  of  antipyrin  was  followed  in  five  minutes  by  roaring 
in  the  ears,  lachrymation,  a  burning  sensation  about  the  neck  and  face, 
precordial  distress,  and  dyspnea.  On  another  occasion  7  grains,  and  later, 
3.5  grains,  produced  a  similar  train  of  symptoms, 

18S8. 
Mayor,  A.     Abs.,  Brit.  Med.  J.,  London,  1888,  2:  787. 

Author  states  that  he  had  repeatedly  observed  instances  in  which  serious 
toxic  symptoms  followed  the  ingestion  of  antipyrin  in  doses  as  small  as 
7.5  grains. 

MoNOD,  L.  Accidents  determines  par  I'absorption  d'une  faible  dose  d'antipyrine. 
Tribune  med.,  Paris,  1888,  20:  113. 

A  dose  of  7.5  grains  of  antipyrin  was  followed  by  symptoms  of  coryza, 
dyspnea,  aphonia,  swelling  of  the  eyelids,  lachrymation,  and  general  weak- 
ness, without  fever  or  eruption. 

1889. 

Beeger,  H.  Ueber  einen  Fall  von  Antipyrinintoxikation.  Therap.  Monatsh., 
Berlin,  1889,  3:  185. 

Ingestion  of  15  grains  of  antipyrin  by  a  patient  22  years  of  age  was  fol- 
lowed by  dyspnea,  palpitation,  swelling  of  the  face,  profuse  salivation, 
increased  secretion  of  tears,  and  perspiration,  and  a  feeling  of  paralysis 
which  lasted  for  several  days. 


LITERATURE    ON    ANTIPYRIN    POISONING.  71 

B..  H.     The  danger  of  antipyrin.     Med.  Rec,  New  York,  ISS9,  36:  431. 

Woman,  facial  neuralgia :  Thirty  grains  of  antipyrin  in  three  equal 
doses,  six  hours  apart,  caused  marked  prostration  and  convulsions. 

Feeny.  M.  H.  Remarkable  action  of  antipvrin  in  renal  disease.  Lancet,  Lon- 
don, 1899,  2:  431. 

Two  cases  of  renal  disease  in  which  antipyrin  in  3-grain  doses  caused 
increased  irregularity  of  heart  and  syncope. 

Hahn,  F.  Ein  Fall  von  Antii>vrinexauthem.  Centrlil.  kiln.  Med.,  Leipzig,  1880, 
10:  849. 

Ingestion  of  0.5  drachm  of  antipyrin  was  followed  by  dysphagia,  cyanosis, 
and  swelling  of  the  lips.    Erythema  developed  the  next  day. 

HucHABD,  H.  Contre-indications  de  Fantipyrine  pendant  la  periode  menstruelle. 
Rev.  gen.  clin.  therap.,  Paris,  1SS9,  3:  52. 

Administration  of  15  grains  of  antipyrin  was  followed  by  cyanosis  and 
symptoms  of  depression. 

NoBTHRUP.  W.  P.  A  case  of  antipyrin  poisoning.  Med.  News,  Philadelphia, 
18S9,  54:  4G1. 

The  administration  of  15  grains  of  antipyrin  to  a  hysterical  woman 
caused  sneezing,  vomiting,  diarrhea,  and  marked  prostration ;  5  grains 
caused  sneezing,  dyspnea,  and  an  urticarial  eruption. 

1Q90. 

Mitchell,  cited  by  Falk,  E.  Ueber  Nebenwirknngen  und  Intoxicationen  bei 
der  Anwendung  neuerer  Arzneimittel.  Therap.  Monatsh.,  Berlin,  1890, 
4:  97. 

The  ingestion  of  1  drachm  of  antipyrin  in  three  doses  at  hourly  intervals 
was  followed  by  iiersistent  vomiting  and  marked  prostration. 

Young,  E.  W.     Poisoning  with  antipyrin.     Med.  Rec.  New  York,  1890,  37:  409. 
Man,  43:  A  dose  of  0  grains  of  antipyrin  with  a  teaspoonful  of  whisky 
an<l  water  was  followetl  by  dyspnea,  vertigo,  dimness  of  vision,  an  urti- 
carial eruption,  and  marked  prostration. 

1©01. 

PoBTO  DE  Cahy.  Syncopes  jtroduites  ]inv  I'antipyrine.  Bui.  soo.  mod.  i)rat., 
Paris,  1891,   p.  29. 

(Jirl,  20:  A  dose  of  15  grains  of  antipyrin  was  followed  by  vertigo  and 
marked  depression.  Two  months  later  a  dose  of  7.5  grains  produced  simi- 
lar symptoms.  riK)ii  a  third  occasion  syncope  followed  the  ingestion  of 
15  grains. 

I'iGNOT,  cite<l  by  Founder,  1892,  p.  495. 

A  s<^'jirlaliiiiform  erupt  ion  and  niaiked  depression  followed  the  ingestion 
of  antipyrin. 

CEBNft.    Accidents  dus  A  I'antipyrine.     .Vorniandie  niM.,  Rouen,  1893,  S:  273. 

fJiri,  n  :  Eaeli  dose  of  aiitiiiyrin  was  follow«'d  liy  vctmiting.  nose  blei'd, 
and  depression. 


72  ACETANILID,    AISTTIPYRIN,    AND    PHENACETIN. 

1894. 

Lepine,  R.     Sur  les  accidents  produits  par  I'antipyrine.     Semaine  med.,  Paris, 
1894,  14:121. 

Woman,  53 :  On  three  occasions  a  5-grain  dose  of  antipyrin  was  followed 
by  enormous  swelling  of  the  lips  and  tongue,  coma,  involuntary  evacuations 
of  bladder  and  bowels,  and  marked  prostration. 

Sutton,   A.     Toxic   svmptoms   induced   by  antipyrin   and   chlorate   of   potash. 
Australas.  Med.  Gaz.,  Sydney,  1894,  13:  43. 

Young  woman,  headache :  A  dose  of  5  grains  of  antipyrin  was  followed 
by  the  appearance  of  a  bright  red  rash  and  symptoms  of  marked  depression. 

1896. 

ScHEEL.     Ein  Fall  von  Antipyrinvergiftung.     Cor.-Bl.   allg.   Mecklenb.   Aerzte, 
Ftostock  (1896),  1893-97,  Nos.  151-187,  p.  389. 

Woman,  50,  headache:  Ingestion  of  8  grains  of  migrainine  was  followed 
by  swelling  of  the  tongue,  upper  lip,  pain  in  the  eyes  and  lachrymation, 
a  scarlatiniform  eruption,  and  marked  prostration. 

1897'. 

DucHENNE.     Intolerance  excessive  pour  Fantipyrine.     Med.  mod.,  Paris,  1897, 
8 :  167. 

The  ingestion  of  12  grains  of  migrainine  was  followed  by  marked  pros- 
tration and  the  appearance  of  an  erythematous  rash  with  the  subsequent 
development  of  blisters. 

Wallace,  F.  G.     Poisoning  by  antipyrin;  recovery.     Lancet,  London,  1897,  1: 
409. 

Woman,  convalescent  from  typhoid :  Administration  of  10  grains  of  anti- 
pyrin in  aromatic  spirits  of  ammonia  and  water  was  followed  by  temporary 
blindness,  a  bright  red  eruption,  dyspnea,  and  great  depression. 

Webster,  E.    Antipyrin  poisoninfg.     Brit.  Med.  J.,  London,  1897,  1 :  458. 

Ingestion  of  5  grains  of  antipyrin  in  a  sedative  mixture  was  followed 
by  great  swelling  of  the  face,  dyspnea,  cyanosis,  an  eruption,  and  marked 
prostration. 

1903. 

Seiler,  D.     Ein  Fall  von  Antipyrin-Intoxikation.     Cor.  Bl.  f.  schweiz.  Aerzte, 
Basel,  1902,  32 :  470. 

Woman,  26,  acute  rheumatism :  After  having  taken  about  3  drachms  of 
antipyrin  in  divided  doses  there  appeared  edema  of  the  face  and  a  scarla- 
tiniform eruption  with  marked  depression. 

1904.. 

Landrieux  et  Rousseau.    Intoxication  par  I'antipyrine.     Bui.  med.,  Paris,  1904, 
18:  357. 

The  ingestion  of  0.5  drahm  of  antipyrin  was  followed  by  very  intense 
dyspnea,  swelling  and  redness  of  the  face,  coryza,  and  prostration. 

190'7. 

Azi&MA.    Sur  un  cas  d'intoxication  par  I'antipyrine.    Toulouse  med.,  1907  (2.  s.), 
9:  111. 

Woman,  42 :  Six  doses  of  antipyrin  of  7.5  grains  each  within  three  hours 
were  followed  by  vertigo,  persistent  vomiting,  unconsciousness,  and  marked 
prostration. 


LITERATURE    ON    AXTIPYRIX    POISONING.  73 

NERVOl  S  SYMPTO:srS. 

In  these  cases  the  nervous  symptoms  appear  to  have  been  very 
prominent.  The  sj^mptoms  varied  Avidelj'^  in  the  different  cases.  For 
example,  there  was  in  one  case  what  appeared  to  be  temporary 
paralysis,  and  in  several,  excessive  restlessness  or  convulsions.  In 
others  there  were  disturbances  of  sensation,  like  numbness,  tingling, 
formication,  and  sensation  of  prickling.  In  still  others  there  were 
disturbances  of  hearing  or  speech,  great  mental  excitement,  excessive 
sneezing,  vertigo,  delirium,  or  coma.  In  one  or  two  instances  the 
symptoms  resembled  those  of  hysteria. 

1888. 

GiQt'EL.     Les  accidents  de  I'antipyrlne.     Gaz.  hebd.  med.,  Paris,  TSSS,  25:  183. 

Ingestion  of  15  gi'ains  of  antipyriu  was  followed  by  itcliing  of  the  gums, 

persistent  sneezing,  and  a  tickling  sensation  in  the  larynx,  causing  cough 

and  hoarseness.     Jhis  was  followed  by  symptoms  of  coryza.     On  another 

occasion  3.75  grains  caused  similar  symptoms,  but  milder  in  degree. 

Peteks,  S.     Poisoning  by  a  ten-grain  dose  of  antipyrine.     Med.  Reg.,  Philadel- 
phia, ISSS,  3:  275. 

Woman,  25,  headache:  Ingestion  of  10  grains  of  antipyriu  was  followed 
by  distressing  nervous  symptoms,  including  pain  in  the  head,  excessive 
sneezing,  swelling  of  the  eyes  and  lachrymation,  and  maniacal  excitement. 

RoBB.  J.  T.     Idiosyncrasy  with  regard  to  antipyrin.     Lancet,  London,  ISSS,  2: 
163. 

Woman,  headache:  A  dose  of  15  grains  of  antipyrin  was  followed  by 
nausea,  sneezing,  symptoms  of  coryza,  dyspnea,  and  aphonia. 

Stur(;e,  W.  a.     Idiosvnerasv  with  regard  to  antipyrin:  A  warning.     Brit.  JMed. 
J.,  London,  1888,"^  1 :  24.3. 

The  ingestion  of  5  grains  of  antipyrin  by  a  young  woman  was  followed 
by  the  appearance  of  an  urticarial  eruption  and  disagreeable  nervous  symp- 
toms, including  excessive  snt^zing,  dyspnea,  profuse  sweating,  coppery 
taste  and  smell,  ringing  in  the  ears,  etc. 

1880. 

IJattkx,  R.  D.,  and  P.okcnham.  T.  J.     A  contribution  to  our  knowledge  of  tiie 
physiological  action  of  antipyrin.     Brit.  Med.  J.,  Loudon,  1881),  1:  1224. 

(1)  In  each  of  3  cases  of  poisoning  by  antipyrin  there  was  great  restless- 
ness, anxiety,  and  giddiness,  and  a  sensation  of  prickling  in  the  feet.  (2) 
A  girl  taking  45  grains  of  antipyrin  daily  for  chorea  became,  on  the  third 
morning,  drowsy,  dizzy,  and  finally  delirious,  with  slow,  labored  breathing. 

1Q92. 

CoiiN,  .M.     Antii»yrlnintoxlcation.     Therap.  Monatsh.,  Berlin,  1S!)2.  (J:  024. 

A  dose  of  7.5  grains  of  antipyriu  was  followed  by  dizziness,  incoherent 
H[>eech,  and  vomiting. 

lHf>.~i. 

LKwr.N.  (;.     I'.crl.  kliii.  VVochensciir.,  1S!),5.  32:  727. 

(1)  Antipyrin  taken  for  beada<-h(!  caus<'d  cotivnlsioiis  and  (ii'lirinin. 
(2)   'I'lie  iiigeHlion  of  antipyrin  was  followed  by  s»ivere  dyspnea. 


74  ACETANILTD,    AFTIPYRIN,    AND    PHENACETIN. 

1904. 

Dancourt,  C.  Un  cas  d'iutoxication  profonde  par  ] 'usage  immodere  de  Fanti- 
pyrine.     Nord.  med.,  Lille,  1904,  10:  89. 

Patient,  55 :  Habitual  use  of  0.5  drachm  of  autipyrin  daily  liad  a  detri- 
mental effect  upon  the  nervous  system,  causing  abolition  of  the  reflexes 
and  slight  paralysis. 

MOUTH   SYMPTOMS. 

In  these  cases  the  toxic  symptoms  were  exhibited  chiefly  by  the 
mucous  membrane  of  the  mouth.  There  was,  in  most  instances,  a 
burning,  prickling  sensation,  w^hich  was  followed  by  swelling  and  the 
development  of  small  blisters  upon  the  tongue,  inside  of  the  cheeks  or 
gums,  with  subsequent  ulceration.  In  most  cases  the  ulcers  healed 
kindly.  In  one  of  the  cases  a  number  of  abscesses  formed  in  the 
mouth. 

X8S9. 

Bourns,  D.  C.  G.  Unusual  effects  of  antipyrin.  Brit.  Med.  J.,  London,  1889, 
2:  818. 

A  dose  of  20  grains  of  antipyrin  was  followed  by  cyanosis  of  the  lips, 
swelling  of  the  tongue,  and  the  development  of  small  ulcers  within  the 
mouth. 

X890. 

Salingkr,  .J.  L.  A  case  of  antipyrine  poisoning,  with  the  formation  of  mem- 
branes in  the  mouth,  and  symptoms  of  Laryngismus  stridulus.  Amer.  J. 
Med.  Sci.,  Philadelphia,  1890    (n.  s.),  99:  489. 

Woman,  53 :  A  dose  of  5  grains  of  antipyrin  was  followed  by  dyspnea,  an 
urticarial  eruption,  swelling  of  the  lips  and  tongue,  coma,  and  symptoms  of 
collapse.  On  the  third  day  a  white  membrane  formed  upon  the  tongue, 
lips,  and  pharynx,  and  soon  after  13  abscesses  the  size  of  a  chestnut  or 
smaller  developed  in  the  mouth.  Ou  two  subsequent  occasions  the  ingestion 
of  5  grains  of  the  drug  was  followed  by  similar  symptoms. 

1S91. 

Veiel.  Ein  seltener  Fall  von  Blasenausschlag  in  Folge  von  Antipyrin.  Arch. 
Dermat.  Syph.,  Wien,  1891,  23:  33. 

Man,  33,  headache:  Ingestion  of  15  grains  of  antipyrin  was  followed  by 
itching  of  the  palms  and  soles,  swelling  of  the  lips,  and  the  formation  of 
blisters  in  the  mouth.  Similar  symptoms  appeared  whenever  the  patient 
took  antipyrin. 

1893. 

GouKiN,  E.     Des  accidents  dus  a  I'antipyrine.     Paris,  1893,  p.  59. 

Ingestion  of  15  grains  of  antipyrin  was  followed  by  swelling  and  ulcera- 
tion within  the  mouth. 

1894. 

Beasch,  M.  Zum  Capitel  der  Antipyrinexantheme.  Therap,  Monatsh.,  Berlin, 
1894,  8:  565. 

Ingestion  of  30  grains  of  antipyrin  was  on  four  occasions  followed  by 
swelling  of  the  lip  with  the  formation  of  blisters  and  the  appearance  of 
white  plaques  on  the  tongue. 


LITERATURE    ON    ANTIPYRIN    POISONING.  75 

1895. 

Senator.     Berl.  klin.  Wochenschr.,  1895,  32:  727. 

Girl,  16 :  Ingestion  of  4.5  grains  of  antipyriu  within  three  days  was  fol- 
lowed by  a  burning  sensation  in  the  eye,  mouth,  tongue,  and  pharynx,  and 
the  appearance  of  vesicles.  At  the  Siiuie  time  au  urticarial  eruption  de- 
veloped upon  the  body. 

IBOO. 

Dalciie.  r.  Accidents  causes  par  I'antipyrine.  Rtomatite  ulcero-membraneuse. 
Bui.  mem.  soc.  med.  hop..  Paris,  1X90  (3  s.),  13:  704. 

Man,  26 :  A  dose  of  15  grains  of  antipyriu  resulted  in  the  appearance  of 
vesicles  in  the  mouth  followed  by  ulceration. 

Steinhardt.  Idiosynkrasie  gegen  Antipvrin.  Therap.  Monatsh.,  Berlin,  1896, 
10:  629. 

The  ingestion  of  15  grains  of  antipyriu  was  followed  by  swelling  of  the 
lower  lip  and  the  development  of  ulcers  within  the  mouth. 

1897-. 

Lyon.  Dermatitis  et  stomatitis  pemphigoides  dues  Ti  I'antipvrine.  Med.  mod., 
Paris.  1897,  8:  167. 

Woman,  .32 :  The  ingestion  of  15  grains  of  antipyriu  was  followed  by  the 
appearance  of  a  pemphigoid  eruption  around  the  knee  and  elbow.  There 
was  also  an  eruption  upon  the  mucous  membrane  of  the  mouth. 

189«. 

Immerwahr.  R.  Ein  Fall  von  Antipyrinintoxication.  Berl.  klin.  Wochenschr., 
1898,  35:  751. 

On  two  occasions  the  ingestion  of  0.5  grain  of  antipyriu  was  followed  by 
the  appearance  of  vesicles  within  the  mouth. 

Martyn,  G.  K.  Stomatitis  following  the  administration  of  antipyriu.  Brit. 
Med.  J..  London,  1898,  2 :  807. 

Ingestion  of  antipyriu  was  followed  by  the  appearance  of  patches  of 
superficial  stomatitis. 

1899. 

Delobel.  Stomato-GIossite  herpetiforme  consecutive  a  I'absorption  d'anti- 
pyrine.     J.  sci.  med.  Lille,  1891>,  1 :  25. 

After  taking  .30  grains  of  antipyrin,  and  again  after  15  grains,  the  patient 
suflfered  from  an  eruption  of  herpetic  vesicles  in  the  mouth. 

lOO.'J. 

Leredde  kt  I'at'trier,  L.  I-^tude  experinicntale  d'une  eruption  medicamenteuse, 
due  Jl  raiitipyrine;  existence  de  lesiims  sanguines.  Compt.  rend.  soc.  l)iol., 
Paris,  1903.  55:  910. 

The  ingestion  of  3  grains  of  jiiilipyrin  was  followed  by  pruritus  of  the 
genital  organs,  an  urticarial  ('rui)tion.  nasal  catarrh,  and  patches  in  the 
mouth  and  upon  the  lips. 

lJ»r).'->. 

LOEBI,,  II.  Seltene  Lokalisafion  cines  Aiitipyrincxantlieiiis.  Med.  Itl.,  WIen, 
19(J.5,  28:  31.5. 

Following  the  Ingestion  of  anlipyrin  tbf  iiilcrior  of  tin-  inoutli  bt-came 
covered  with  small  blisters,  which  burst,  giving  rise  to  coiilluent  ulceratiou. 


76  ACETANILID,    ANTIPYRIN,    AND   PHENACETIN. 

1906. 

Levin,   E.     Zur  Kenntniss  der   Migrjininvergiftnng.     Berl.   kiln.    Wochensclir., 
1906,  43:  766. 

Ingestion  of  15  grains  of  migrainine  was  followed  by  swelling  and  ulcera- 
tion of  the  mucous  membranes  of  the  mouth  and  profuse  salivation. 

EYE   SYMPTOMS. 

Under  this  heading  are  included  the  cases  in  which  the  acuity  of 
vision  was  diminished  or  the  sight  temporarily  lost,  and  also  the  cases 
characterized  by  the  symptoms  of  coryza,  with  swelling  of  the  lids,^ 
lachrymation,  and,  in  some  instances,  photophobia.  The  symptoms 
in  most  cases  appeared  promptly,  sometimes,  it  seemed,  almost  as 
soon  as  the  drug  reached  the  stomach. 

1906. 

HoTz,  F.  C.    A  case  of  autipyrin  amaurosis  induced  by  one  hundred  and  thirty 
grains  taken  in  forty-eight  hours.     Arch.  Ophth.,  New  York,  1906,  35 :  160. 

Man,  33 :  Had  taken  antipyretics  for  pain  for  three  years.  One  hundred 
and  thirty  grains  of  antipyrin  within  forty-eight  hours  caused  his  sight 
to  become  dim,  and  within  two  days  it  was  lost  completely.  It  returned 
slowly  and  in  two  months  he  was  practically  well  again. 

Inouye,   M.     Antipyrin   keratitis.     Ophthalmol.,    Milwaukee,    1905-6,    2:  618. 

Woman,  48 :  Ingestion  of  25  grains  of  antipyrin  in  2  doses  was  followed 
by  the  development  of  41  superficial  infiltrations  upon  the  cornea,  25  upon 
the  right  and  16  upon  the  left.  The  author  also  reviews  a  case  reported 
by  Mizno,*  in  which  ulcers  developed  upon  the  cornea  as  a  result  of  the 
ingestion  of  antipyrin. 

GENITO-URINARY    SYMPTOMS. 

Under  this  head  are  grouped  the  cases  in  which  the  toxic  effects  of 
antipyrin  were  exhibited  chiefly  in  some  part  of  the  genito-urinary 
tract.  The  symptoms  presented  were  principally  albuminuria,  sup- 
pression or  incontinence  of  urine,  or  symptoms  of  urethro- cystitis. 

18S4. 

MtJLLER,  F.     Beobachtungen  iiber  Antipyrin.     Centrbl.  klin.  Med..  Leipzig,  1884, 
5:  569. 

Drowsiness  and  involuntary  micturition  appeared  in  two  cases  after  the 
ingestion  of  antipyrin. 

1S85. 
Haven,  H.  C.     Discussion  of  Mason's  paper.      (1885.)     p.  538. 

Infant :  Ingestion  of  at  least  four  10-grain  doses  of  antipyrin  at  inter- 
vals of  half  an  hour  caused  vomiting  and  complete  suppression  of  urine 
for  over  twenty-four  hours. 

"  Nihon-Gankwa-Gakkwai-Zasshi,  1904,  vol.  S,  No.  11. 


LITERATURE    ON    ANTIPYRIX    POISONING.  77 

1887. 

DE  TuLLio,  P.     L'antipiriiia  iiel   reuiiiatisiuo  i;rticoIan>  acuto.     Prosresso  iiied 
Napoli,  1887,  1 :  913. 

The  ingestion  uf  antipyriii  liy  a  juitieiit  snflferiug  from  articular  rheiinia- 
tisiu  was  followed  by  a  Iransieiit  alhmiiiiuiria. 

1888. 

KouLiN,   L.     Observation   d'accideuts  febriles  produits   i)ar    raiitii)yrine.      liiil. 
mem.  see.  nied.  prat.,  Paris,  1888,  p.  478. 

Ingestion  of  7.5  grains  of  antipyrin  hourly  for  four  hours  was  followed 
by  a  severe  chill,  delirium,  vomiting,  and  suppression  of  the  urine. 

1801. 

Biggs.  H.  M.     Notes  on  a  case  of  poisoning  l)v  antipyriue.     New  York  Med.  J., 
1891,  53 :  35. 

Man,  35,  headache:  Soon  after  the  ingestion  of  60  grains  of  antipyrin 
within  thirty  hours  the  urine  became  darii  olive-green  in  color.  It  con- 
tained a  small  quantity  of  albumin  and  a  few  casts.  Secretion  scanty. 
Symptoms  disappeared  in  the  course  of  two  or  three  days.  No  evidence 
of  previous  renal  disease. 

Tompkins.  E.  I..     Albuminuria  caused  bv  antipyriue.     Virginia  Med.  Month., 
Richmond,  1S91-92,  18:  105. 

Man,  locomotor  ataxia  :  Took  for  pain  each  night  about  GO  grains  of 
antipyrin.  Entered  the  hospital  with  edema  of  the  legs  and  eyelids.  Tlie 
urine  was  so  full  of  albumin  that  it  solidified  on  boiling.  Albumin  was 
abundant  in  the  morning  and  scanty  in  the  evening.  When  the  drug  was 
discontinued  the  albuminuria  disappeared  and  the  edema  diminished. 

1895. 

IvAMOs,  D.     All)uminui-ia  produ/.ida  por  altas  doses  de  autii)yrina.     Hrazil-med.,     ' 
Kio  de  Janeiro,  189.5.  »:  233. 

i8or. 

Spanoudls.  .1       Dangers  de  ranliiiyriue  dans  Ferysipele.     Seuiaiue  uied.,  I'aris, 
1SU7,  17-  42. 

Three  cases  in  wliich  the  ingestion  of  antit)yrin  was  followed  by  anuria, 
with  great  restlessness  and  marlied  depression.  One  case  tcnuinated  in 
death. 

1808. " 

liKSMKK.     liMl.  soc.  franc,  dermat.  syph.,  Paris,  1898,  0:  193. 

An  lntens«'  general  urticaria  followed  the  ingestion  (tf  anlipyriu,  and  an 
autifiyrin  tampon  inserted  for  er>istaxis  caused  vesication  and  symptoms  of 
nrethn»-cystitis. 

SYMPTOMS    OK    COKYZA. 

1888. 
'J'avi.ok,  II.  c;.     Idiosyncrasy  to  autipyriu.     J'>rit.  .Med.  .1..  Loudon,  1S8S,   1  :  (»9.5. 
Woman,  lieadache:  On  two  occasions  the  iugeslion  of  autipyriu   was  Col 
lowed  by  symi»tomH  of  coryza  and  severe  paroxysms  of  cougiiiiig. 


78  ACETAN'ILID,    ANTIPYEIN,    AND    PHEN-ACETIN. 

1897. 

Geoll  et   Meuniee.      Intoxication   par   I'antiprine.     Daupliine   med.,    Grenoble, 
1897,  21:  38. 

The  ingestion  of  22.5  grains  of  antipyrin  was  followed  by  symptoms  of 
coryza. 

1903. 

AxBABEL,     Accidents  dus  a  I'antipyrine.     Rev.   gen.   clin.   tlaerap.,   Paris,   1903, 
17:  612. 

On  two  occasions  tlie  ingestion  of  a  7.5-grain  dose  of  antipyrin  was  fol- 
lowed by  coughing,  burning,  and  dryness  within  the  mouth,  and  symptoms 
of  severe  coryza. 

3IISCELLANEOUS. 

1888. 

Brandenberg,  F.     Nebenwirkung  des  Antipyrins.     Cor.-Bl.,  f.  schweiz.  Aerzte, 
1888,  18:  611. 

Man,  acute  articular  rheumatism :  Ingestion  of  1.5  grains  of  antipyrin 
was  almost  immediately  followed  by  odontalgia,  severe  otitis,  and  lachry- 
matiou.  On  another  occasion  one-half  of  the  above  dose  produced  similar 
symptoms. 

1889. 

TiTCZEK,    F.      Schwere   Antipvrinvergiftung    bei    einem    Kinde.      (Antipyrinepi- 
lepsie.)     Berl.  klin.  Wochenschr.,  1SS9,  26:  373. 

Boy,  4,  whooping  cough :  Antipyrin,  18  grains  in  3  doses  daily  for  three 
weeks,  was  followed  by  vomiting,  drowsiness  passing  into  coma,  convul- 
sions, and  the  appearance  of  a  macular  erj'thema. 

1890. 

DuFFUs,  J.  C.  G.     Parotitis  caused  by  antipvrin.     Brit.  Med.  J.,  London,  1890, 
2:  733. 

Young  woman,  influenza :  A  dose  of  10  grains  of  antipyrin  was  followed 
by  dyspnea  and  swelling  of  the  parotid  glands. 

1891. 

CoMBEMALE.     I'n  cas  d'autipvrinisme  chronique.     Bui.  med.  nord,  Lille,  1891, 
30:  304. 

A  case  of  persistent  use  of  antipyrin  in  which  the  patient  took  from  15 
to  30  grains  daily  for  four  years. 

Verneuil.     Gangrene  partielle  du  pied,  consecutive  a  des  injections  hypoder- 
miques  d'antipyrine.     Bui,  acad.  med.,  Paris,  1891  (3.  s.),  26:  602. 

Man,  39.  neuralgia :  Gangrene  followed  the  hypodermic  injection  of 
antipyrin. 

1893. 

Cappelletti,  L.     Un  caso  di  autipirinomania.     Riv.  sper.  di  freniat.,  Reggio- 
Emilia,  1893,  19:  100. 

Mania  for  antipyrin  in  a  neurotic  girl  aged  23.  Took  small  doses  for 
headache,  and  gradually  increased  the  amount  up  to  2  drachms  daily, 
causing  increase  in  the  severity  of  the  headach.es,  anorexia,  hysterical 
convulsions,  and  symptoms  of  depression. 


LITERATURE    ON    PHENACETIN    POISONING. 


79 


1S95  . 

Gonzalez   y   Campo,   J.      Iiuoxicacion    por    la    aiitipirina    a    tlosis   terapeutica. 
Rev.  de  med.  y  cirug.  pnict.,  Madrid,  1895,  36:  201). 

Case  in  wliicli  the  poisonous  effects  of  antipyriii  may  have  l)t'en  brought 
about  by  a  cumulative  action  due  to  impei-fect  elimination. 

1S97-. 

Papillox,    (;.    E.      Note    sur    iiii    cas    rare    de    dermatoneuroso    consr^cutive    i\ 
I'ingestiun  d'antipyrine.     Echo  med.  nord,  Lille,  1S97,  1 :  97. 

Girl,  19:  Habitual  use  of  antipyrin.  Gradually  increased  the  amount 
until  she  was  taking  from  1  to  1.5  drachms  daily.  The  symptoms  resem- 
bled those  of  ulcer  of  the  stomach. 

ACETPHENETIDIN  (PHENACETINi. 


INTUODUCTOKY   RESl  MK. 

Following  is  a  list  of  the  recorded  cases  of  poisoning  by  acetphe- 
netidin  (phenacetin)  from  1887  to  the  close  of  the  year  1907,  with 
a  brief  abstract  of  each  case.  During  this  period  70  or  more  cases 
were  reported  by  41  observers.  As  already  stated,  it  is  practically 
impossible  to  determine  the  number  of  the  cases  with  accuracy,  owing 
to  the  indefinite  character  of  some  of  the  reports.  Of  the  total  num- 
ber of  cases,  3,  or  4.2  per  cent,  are  reported  to  have  terminated  fatally. 
This  number,  70,  is  notably  less  than  the  reported  number  of  cases  of 
poisoning  by  either  acetanilid  or  antipyrin,  and  this  fact  tends  to  sub- 
stantiate the  common  belief  that  of  the  three  drugs  acetphenetidin  is, 
under  ordinary  circumstances,  the  least  liable  to  produce  ill  effects. 

The  number  of  cases  of  poisoning  reported  in  each  year  since  the 
introduction  of  acetphenetidin  as  a  remedial  agent,  together  with  the 
number  of  observers,  is  shown  in  the  following  table: 

Caxr-f  of  tiff'tj/lif'nrtiilin  (phenacetin)   poi-sonhnj  rcportrd  <innH<iUy,  JHH7-1!)07. 
[No  cast's  reported  for  yi-ars  omitted.] 


Year. 

Number 
of  cases. 

Number 

of 
observers. 

Year. 

Number 
of  cases. 

Number 

of 
observers. 

Year. 

Number 
of  cases. 

Number 

of 
observers. 

1887 

1888 

1889 

1 
23 
11 

1 

10 
0 
3 
2 
2 

1893 

1894 

18% 

18% 

1899 

1901 

2 
3 
6 

1 
1 

1 

1 
3 
4 
1 
1 
1 

1903 

1904 

1905     . 

1 
2 
2 

1 

1 

2 
o 

Xfm'.'.'.'.'.'.'.'.l               6 

1907 

Total. 

1 

1892 

' 

70 

41 

It  will  be  seen  that  23,  or  32.8  per  cent,  of  all  tlie  cases  were  reixjitcd 
during  the  year  following  the  advent  of  acetpliciictidiii  as  a  mcdiciiu^ 
in  1887,  and  that  40,  or  .■>7.1  [)er  cent,  wei'c  r('j)ort<'(l  (hiring  (he  years 
1888,  1889,  and  1890.  Tlie  large  proporlion  of  cases  reported  during 
this  period  was  undoubtedly  due  in  part,  as  in  case  of  acetanilid  aiul 
antipyrin,  to  the  fart  that  at  this  time  the  depressing  effect  of  ncvl- 


80  ACETANILID,    ANTIPYRIN,    AND    PHENACETIN. 

phenetidin  was  not  fully  appreciated,  and  it  was  administered  more 
or  less  freely  in  asthenic  as  well  as  sthenic  affections.  This  method  of 
administration  resulted  in  the  production  of  ill  effects  in  not  a  few 
cases.  After  the  year  1890  the  number  of  cases  of  poisoning  reported 
annually  was,  upon  the  average,  only  two  or  three  cases,  and  the 
number  appears  to  have  decreased  rather  than  increased  as  the  years 
passed. 

The  ill  effect  which  appears  to  occupy  the  place  of  greatest  im- 
portance in  the  recorded  cases  is  general  systemic  depression.  This 
symptom  appears  to  have  been  present  in  27,  or  38.5  per  cent,  of  the 
cases.  In  12  cases,  or  17.1  per  cent,  it  amounted  to  actual  collapse, 
and  in  15,  or  21.4  per  cent,  it  was  present  in  a  milder  form.  Cyanosis 
was  reported  in  34.3  per  cent  of  the  cases,  and  the  comparatively^  fre- 
quent occurrence  of  this  sjanptom  indicates  the  close  pharmacological 
relationship  which  exists  between  acetphenetidin  and  acetanilid. 
Skin  affections  of  various  kinds  were  noted  in  30  per  cent  of  the  cases, 
dyspnea  in  14.3  per  cent,  and  disturbances  of  the  functions  of  the  kid- 
neys in  10  per  cent. 

ABSTRACTS   OF  ACETPHENETIDIN   (PHENACETIN)   CASES. 

ISST". 

KoBLER,  a.     Das  Acetphenetidin  als  Antipyretic-nm.     Wien.  uied.  AVochensclir., 
1887,  37:  868. 

In  a  pMhisica]  patient  two  doses  of  phenacetin  of  4.5  grains  each  within 
two  hours  caused  the  patient's  temperature  to  fall  rapidly  to  95°  in  the 
rectum,  with  profuse  perspiration  and  a  feeling  of  chilliness. 

ISSS. 

Cakslaw,  J.  H.    Phenacetine  as  an  antipyretic.     Glasgow  Med.  J.,  1888,  30:  64. 
A  single  dose  of  5  grains  of  phenacetin  caused  collapse  in  three  out  of 
five  tubercular  patients  to  whom  the  drug  was  administered. 

Cattani,   G.     La  fenacetina.     Gazz.  med.   ital.  lomb.,   Milano,  1888,   48    (9  s. 
vol.  1)  :  455. 

The  author  had  twice  observed  hematuria  and  nephritis  following  the 
ingestion  of  phenacetin.    Pie  had  also  observed  an  acne-like  eruption. 

HoppE,  H.    Ueber  die  Wirkung  des  Phenacetin.    Therap.  Monatsh.,  Berlin,  1888, 
2:  160. 

(1)  Anemic  girl  took  19  grains  of  phenacetin,  and  after  four  hours  a 
second  powder.  This  was  followed  bj'  dizziness,  shivering,  yawning,  chilli- 
ness, blueness  of  the  nails,  and  some  nausea.  (2)  Woman,  44:  The  in- 
gestion of  15  grains  of  phenacetin  for  headache  was  followed  by  chills  and 
dizziness.  (3)  Thirty  grains  of  the  drug  taken  by  a  healthy  student  were 
followed  by  persistent  yawning,  nausea,  insomnia,  general  weakness,  feeble 
pulse,  and  inability  to  stand.  The  symptoms  lasted  for  three  hours.  (4) 
Woman,  26:  The  ingestion  »of  15  grains  of  phenacetin  for  headache  was 
followed  in  fifteen  minutes  by  chilliness,  coldness  of  the  extremities,  severe 
palpitation,  and  a  sensation  of  intense  fear.  The  symptoms  passed  off  after 
six  hours. 


LITERATURE    OX    PHEXACETIX    POISOXIXG.  81 

V.  Jaksch,  R.     Ueber  die  neiieivn  Antipyretica  und  iiite  Wiikun-r  am  Krar.kcn- 
bette.    Tlierap.  Mouatsh.,  Berliu,  1888,  2:  189. 

Author  had  observed  that  the  adnimistration  of  1.5  to  3  grains  of  phe- 
nacetiu  to  children  iu  a  nuuiber  of  cases  produced  profuse  sweating,  severe 
cyanosis,  and  even  symptoms  of  collapse. 

LiXDMAXX.       T'nangenehnie,     bedrohlicbe     Xebenwirkuugen     des     Phenaoetiu. 
Therap.  Monatsh.  Berlin,  1888,  2:  3UT. 

Woman,  .34  :  Soon  after  taking  l.^>  grains  of  phenacetin  she  felt  dizzy, 
cold,  and  nauseated.  Her  headache  became  worse,  and  after  three  hours 
she  took  another  phenacetin  powder.  This  was  followed  by  an  aggravation 
of  the  symptoms:  the  nausea  and  sensation  of  chilliness  increased,  the 
hands,  lips,  and  cheek.s  were  deep  blue,  and  there  was  cold  perspiration  and 
dyspnea. 

Mahxert,    F.     T'eber   Phenacetin   voni   klinisrhen   und    physiologischen   vStand- 
r>unkte.     Deutsche  med.  Wochenschr.,  Leipzig,  1888,  l4:  10.51. 

A  nervous  woman,  after  taking  lo.o  grains  of  phenacetin  for  headache, 
developed  a  well-marked  urticaria  on  the  face  and  chest. 

>L\sirs.     Contribution  tl  Tetude  de  proprietes  therapeutiques  de  la  phenacetine. 
Bull.  acad.  roy.  med.  belg.,  Bruxelles,  18SS  (4  s.).  2:  81.5. 

(1)  Girl,  10,  typhoid:  Was  given  7.5  grains  of  phenacetin  at  3  and  at  8 
o'clock  a.  m.  About  an  hour  after  the  second  dose  she  comi)lained  of  thor- 
acic oppression,  a  sensation  of  intense  heat,  marked  prostration,  and  deep 
cyanosis.  The  cyanosis  passed  off  on  the  following  day.  On  the  preceding 
day  the  patient  had  taken  30  grains  of  phenacetin  without  ill  effect.  (2) 
(iirl.  1.5.  typhoid:  Five  hours  after  taking  two  doses  of  phenacetin  of  3.75 
grains  each  the  patient's  tenipei'ature  rose  raiiidly  with  a  severe  chill. 
There  was  also  slight  cyanosis  of  the  extremities.  (3)  Woman,  24:  The 
Ingestion  of  three  doses  of  phenacetin  of  7.5  grains  each  was  followed  after 
four  hours  by  a  severe  chill  and  cyanosis  of  the  lips  and  skin  around  the 
eyes.  (4  and  5)  In  two  instances  the  ingestion  of  phenacetin  by  tubercular 
patients  produced  ill  effects,  principally  chills  and  cyanosis.  In  one  case 
the  dose  was  15  grains,  and  in  the  other  (j  grains. 

MuxLEB,  F.     Ueber  Acetphenetidiu.     Therap.  Monatsh.,  Berlin,  1888,  2:  355. 

Author  observed  cyanosis  and  methemoglobinuria  in  two  patients  who 
were  taking  from  1.5  to  2  drachms  of  phenacetin  daily. 

RuMPF.     Ueber  das  Phenacetin.     Berl.  klin.  Wochenschr.,  1888,  25:  45!» 

The  ingestion  of  15  grains  of  phenacetin  was  followed  on  several  succes- 
sive days  by  a  feeling  of  thoracic  oppression  and  slight  dyspnea. 

Valextix.  a.     Ein   Fall    von   Phenacetinexanthem.     Therap.   Monatsli..   P.erliii. 
1S88,  2:  :j;jo. 

Two  hours  after  taking  a  dose  of  15  grains  of  phenacetin  the  patient  felt 
a  sensation  of  heat  and  i>y  the  next  day  the  entire  skin  was  covered  witli 
red  HiKjts.  The  eruption  was  especially  marke<l  upon  the  extremities.  It 
disappj-ared  after  tweiity-f'nir  hours. 

1HM1». 

IIk.x.scmkx,   S.    K.     '^>m   s.   k.   konlriir    vcrkan    iif   fcbfiiin-dcl.      i  psaia    L;ik:n(  .' 
Forh.,  1S.H8-80,  24:  203. 

Author  observed  in  a  patient  a  rise  nf  tfinpi-i'atinc  after  llif  adiiiiiiisi  lii- 
tlon  of  phenacetin. 

82.311)— P.ull.  12!V— 0!) 0 


82  ■  ACETANILID,    ANTIPYEIN,    AND    PHENACETIN. 

HiRSCHFELDER,  L.  Beiti'ag  zur  Wirkuug  ties  Plieuacetius.  Deiitsches  Arch, 
kliu.  Med.,  Leipzig,  1S88-89,  44:  434. 

The  ingestion  of  pheuacetin  was  followed  by  the  appearance  of  red  con- 
fluent macules,  accompanied  by  a  sensation  of  burning  and  prickling.  The 
symptoms  disappeared  on  the  following  day. 

HoLLOPETER.  W.  C.  Phenacetiue  poisoning.  Med.  News,  Philadelphia,  1889, 
55:  335. 

Woman,  30 :  Took  three  doses  of  pheuacetin  of  7.5  grains  each  within 
six  hours.  She  passed  into  a  state  of  collapse,  with  severe  precordial  pain, 
great  dyspnea,  lividity  of  the  skin,  and  great  restlessness.  The  cyanosis 
persisted  for  three  days. 

HoRVATH,  A.  A'datok  a  pheuacetin  hetasahoz.  Orvosi  hetil.,  Budapest.  1889, 
33:  474.     (Abs.  Pest,  med.-chir.  Presse,  Budapest,  1889,  25:  1134.) 

Report  of  two  cases  in  which  the  use  of  pheuacetin  was  followea  by  an 
eruption  upon  the  skin. 

Oeffinger.  Eine  eigenthiimliche  Nebenwirkung  des  Pheuacetin.  Aerztl.  Mitth. 
Baden,  Karlsruhe,  1889,  43:  110. 

The  ingestion  of  30  grains  of  pheuacetin  in  two  doses  with  an  interval 
of  three  hours  caused  edema  of  the  lower  eyelids.  A  few  days  later  45 
grains  in  three  doses  caused  edema  of  the  face  and  fingers. 

Tripold,  F.  Ueber  die  therapeutische  Wirkung  des  Pheuacetin  und  Thalliu. 
Wien.  klin.  Wochenschr.,  1889,  2 :  151,  178. 

Author  states  that  in  his  experience  doses  of  4.5  grains  of  pheuacetin 
had  produced  deep  cyanosis  of  the  face  and  hands  and  profuse  perspiration 
in  children  suffering  from  tuberculosis.  In  a  case  of  pneumonia  a  dose  of 
4.5  grains  caused  severe  collapse,  with  cyanosis.  Even  3  grains  caused 
chills,  collapse,  and  cyanosis  in  two  cases  in  children. 

1890. 

CoLLiscHONN.  Pheuacetin  als  Antirheumaticum.  Deutsche  med.  Wochenschr., 
Leipzig,  1890,  16:  97. 

The  ingestion  of  phenacetiu  was  followed  by  repeated  vomiting,  so  that 
the  administration  of  the  drug  had  to  be  stopped. 

RiFAT.  Traitement  du  rhumatisme  aigu  et  biennorrhagique  par  la  phenac^tine  k 
haute  dose.    Bui.  gen.  therap.  (etc.),  Paris,  1890,  118:  410. 

(1  and  2)  In  two  cases  pneumonia  and  tuberculosis,  respectively,  doses 
of  4.5  grains  of  pheuacetin  caused  profuse  perspiration,  a  tendency  to 
syncope,  and  great  restlessness.  (3)  In  a  case  of  typhoid  fever,  cyanosis 
followed  the  administration  of. large  doses  of  pheuacetin.  (4)  Woman,  65, 
articular  rheumatism,  with  arteriosclerosis :  The  ingestion  of  75  grains  of 
pheuacetin  daily  was  followed  on  the  fourth  day  by  the  appearance  of 
uremic  symptoms.  There  were  vomiting,  severe  dyspnea,  fear,  and  almost 
complete  suppression  of  the  urine. 

Ubaldi,  a.  Suir  aumento  dell'acido  solforico  accoppiato  nelle  urine  in  seguito 
alia  somministrazione  di  fenacetina.  Azione  tossica  della  fenacetina. 
Riforma  med.,  Napoli,  1890,  6  (1)  :  752. 

1891. 

Demme.  Ueber  die  Wirkung  und  Dosirung  der  hauptsachlisten  neueren  Anti- 
pyretica,  mit  Beziehung  auf  das  Kindesalter.  Therap.  Monatsh.,  Berlin, 
1891,  5:  160. 

Author  had  observed  an  eruption  resembling  that  of  measles,  and  cya- 
nosis of  the  cheeks  and  mucous  membranes  in  children  after  the  use  of 
pheuacetin. 


LITERATURE    OX    PHEXACETIX    POISONING.  83 

Hare.  H.  A.     Fever:   Its  pathology  and  tie:ituient  by  .iiitiiiyretics.     ISOI.  Phila- 
delphia aud  Loudou,  p.  122. 

The  author  mentions  two  eases  in  which  the  ingestion  of  H-grain  doses  of 
phenacetin  was  followed  by  the  aiipearante  upon  the  skin  of  large  wheals, 
like  those  observed  in  urticaria. 

Fernandez    de    Ibarra.    A.    M.     In    caso    de    envenenauiiento   eon    fenacetina ; 
curacion.     Gao.  uied.  catal..  Barcelona,  1892,  15:  229. 

TiNGLEY.   W.  K.     Peculiar  vasomotor  disturbance  after  the  administration   of 
phenacetlue.     Med.  Rec,  New  York.  1X92,  42:  .341. 

The  author  had  observed  three  cases  with  almost  identical  symptoms.  In 
each  of  them  phenacetin  alone  i»roduced  no  disturbance,  but  if  champagne 
were  taken  in  addition,  even  after  the  lapse  of  some  hours,  the  patient's 
face  became  flushed,  the  eyes  suffused,  and  the  conjunctiva  bright  red. 
White  spots  appeared  irregularly  over  the  neck,  face,  and  chest,  and  vertigo 
was  present.  Whisky,  brandy,  and  claret  alone  did  not  produce  these 
effects. 

1893. 

Illoway,  H.     Does  phenacetin   possess  convulsivant  jiroperties?     Me<I.   News, 
Philadelphia,  1S93,  G3:  240. 

Report  of  two  cases  in  which  5  grains  of  ])henacetiu  i»roduced  typical 
hystero-epileptic  convulsions  in  women. 

1©94. 

Harold.    J.     Unpleasant    effects    of    phenacetin.     Practitioner,    London.    1S94, 
53:  444. 

The  patient,  a  woman,  took  from  o  to  8  doses  of  phenacetin  of  10  grains 
each  within  twenty-four  hours.  Almost  immediately  she  complained  of 
palpitation  of  the  heart ;  her  face,  except  the  bridge  of  the  nose,  became 
scarlet ;  her  pulse  became  very  rapid,  and  she  suffered  from  headache  and 
shortness  of  breath. 

Knowles,  F.  E.     Symptoms  of  poisoning  from  a  probable  overdose  of  phenace- 
tine.    Med.  Rec.,  New  York,  1894,  46:  504, 

Patient  took  headache  powders  of  unknown  composition,  and  then  10 
grains  of  phenacetin.  There  followed  a  chill,  prosti'ation  with  marked 
cardiac  depression,  cyanosis,  particularly  of  the  extremities,  and  cold  per- 
spiration. The  pulse  was  40  and  scarcely  j)erceptible  at  the  wrist.  Recov- 
ery after  three  hours. 

Davis.    .7.    S.     A    report   of  three   ca.'ses   of   addiction   to   coal-tar   derivatives. 
Amer.  Med.  and  Surg.  P.ul.,  1894,  7:  1490. 

Woman  :  Had  I>een  addicted  to  the  phenacetin  hai)it  for  about  seven 
months,  daily  quantity  being  between  lij  and  20  grain.s.  Addiction  was 
discovered  by  her  husband  when  her  supply  of  the  drug  gave  out  and  the 
local  pharmacist  also  ran  out  of  a  su[iply  temporarily.  Violent  convulsive 
and  hysterical  seizures  followed  and  continued  until  phenacetin  was  secured 
for  her.  Pulse.  170,  and  very  weak.  Resjiiration,  .30,  spasmodic.  Pnr)lls 
widely  dilated;  pallor,  cold  i»erspirafion.  She  had  more  than  a  dozen  con- 
vulsions  and  vomit«'d  freely.  P.eforc  beginning  the  habit  she  was  "a 
healthy,  buxom  conniry  girl."  Kxaniination  made  after  llic  !i1ta<-k  above 
dewribed  showed  some  anemia,  compl'-xioii  bad.  circulation  weak,  pulse 
124,  restlesH  and  ti'oublcd   sleep,   impaired   digest  ion.   occasional   vertigo. 


84  ACETANILID,    ANTIPYRIN,    AND    PHENACETHST. 

Cekna,  D.     Plienacetiu  as  a  toxic  agent.     Tr.  Texas  Med.  Assoc,   Galveston, 
1895,  p.  126. 

Infant,  5  days  old,  was  given  seven  2-grain  phenacetin  powders  witliin 
two  days.  It  became  fretful,  weak,  and  eyanosed.  On  the  next  day  the 
conjunctiva  was  jaundiced,  the  skin  eyanosed,  and  the  child  very  restless. 
On  the  day  following  there  was  extreme  cyanosis,  and  bloody  urine  was 
passed  in  large  quantity. 

Kronig,     G.     Phenacetin-Yergiftung     mit     todtlichem     Ausgang.     Berl.     klin. 
Wochensehr.,  1S95,  32:  99S. 

Boy,  IT :  After  taking  15-grain  doses  of  phenacetin  for  headache  for 
three  weeks,  a  dose  caused  vomiting,  followed  on  the  next  day  by  prostra- 
tion, cyanosis  of  the  face,  weak  pulse,  and  diarrhea.  Jaundice  followed, 
and  the  cyanosis  spread  to  the  extremities.  The  urine  consisted  of  almost 
pure  blood.     Death  occurred,  after  two  days,  from  methemoglobinemia. 

Lackie,  J.  L.     Note  on  phenacetin  as  causing  dyspnoea  and  orthopucea.     Med. 
Press  and  Circ,  London,  1S95,  60 :  208. 

(1)  Dyspnea  and  great  restlessness  followed  the  ingestion  of  phenacetin 
everj-  two  hours  in  15-grain  doses.  (2)  The  ingestion  of  20  grains  of 
phenacetin  every  two  hours  caused  marked  dyspnea,  which  lasted  for  one 
hour. 

West,  R.  M.     Two  cases  of  phenacetin  rash.     Lancet,  London,  1895,  1  :  91. 

(1)  Ingestion  of  two  5-grain  tabloids  of  phenacetin  by  a  man  28  years 
of  age  was  followed  in  three  hours  by  the  appearance  of  a  scarlatiuiform 
rash  upon  the  face,  chest,  and  arms.  It  disappeared  in  two  hours.  (2)  A 
young  woman  took  phenacetin  in  doses  of  from  5  to  15  grains  for  neuralgia. 
On  each  occasion  an  urticarial  rash  appeared,  chiefly  upon  the  face  and 
neck,  after  a  lapse  of  one  or  two  hours. 

1896. 

Betts,  W.  a.     a  case  of  phenacetin  idiosyncrasy.     Brit.  Med.  .!.,  London,  1896, 
.     1:  146. 

Patient  took  8  grains  of  phenacetin  every  three  hours  for  headache. 
After  the  third  dose  he  felt  very  ill,  and  his  face  became  pale.  This  was 
followed  by  shivering,  dyspnea,  cold  perspiration,  and  the  development  of 
wheals  on  the  back  of  the  hands  and  on  the  right  shoulder.  The  face  was 
of  a  mahogany  color  and  swollen.     Dread  of  death.     Recovery. 

1S99. 

Gtjleke,  H.     Taubheit  in  Folge  von  Phenaeetinmissbrauch.     Zts.  prakt.  Aerzte, 
Frankfurt,  1899,  8:  765. 

Male,  48 :  Ingestion  of  10.5  grains  of  phenacetin  every  two  hours  until 
10  doses  had  been  taken  caused  cyanosis  and  complete  deafness. 

1901^ 

KiBBE,  M.   E.     Ecchymotic  spots  and  pruritus  due  to  phenacetin.     Occidental 
Med.  Times,  San  Francisco,  1901,  15:  371. 

Woman,  50 :  Ingestion  of  six  5-grain  powders  of  phenacetin  during  the 
evening  and  morning  caused  itching  of  skin  over  abdomen  and  limbs.  On 
the  fourth  day  large  areas  of  ecchymosis  appeared  on  the  inner  surface  of 
each  thigh,  and  smaller  ones  on  the  abdomen  and  extensor  surfaces. 


LITERATURE    OX    PHEXACETIN    POISONING.  85 

1903, 

White.  A.  T.  A  case  of  acute  dysentery,  in  which  deatii  occurred  from  acute 
cardiac  dilatation  probably  due  to  chronic  phenacetin  poisoning.  J.  Trop. 
Med..  London.  100.3.  6:  176. 

The  increstion  of  about  .3.000  grains  of  phenacetin  in  H-grain  doses  within 
sixty  days  for  fever  was  accouii)anied  by  great  depression  and  a  rapid 
dihition  of  the  heart  followed  by  death.  The  result  may  fairly  be  attrib- 
uted to  the  inordinate  use  of  the  dru.g. 

1004. 

Laurexce.  S.  M.  Case  of  poisoning  bv  phenacetin  and  antikannrla.  P.rit. 
Med.  .J..  London.  1004.  1:  545. 

The  ingestion  of  75  grains  each  of  phenacetin  and  antikanniia  was  fol- 
lowed by  vomiting  and  malaise.  The  face  became  pinched  and  pale,  and  the 
expression  anxious.  The  eyes  were  small  and  the  lips  and  fingers  purple, 
^larked  prostration  with  cold  perspiration. 

LoBL,  V.  Aspirin-('-s  phenacetinmergezesek.  (Aspirin  and  phenacetin  poison- 
ing.)    Budapest!  orv.  u.isrig..  1004.  2:  803. 

HiRSCHFELD,  M.  Eiu  Fall  von  chronischer  Phenacetin-Vergiftung.  Deutsche 
med.  Wocheuschr.,  Leipzig,  1005,  31:  66. 

The  ingestion  of  phenacetin  for  headache  was  followed  by  the  appearance 
of  an  eruption  of  petechial  spots  upon  the  legs,  followed  in  the  cour.se  of 
a  week  by  ulceration.  The  ulcers  healed  rapidly  when  the  drug  was  dis- 
continued, and  appeared  again  after  another  dose  of  22.5  grains. 

Meurice,  J.  Contribution  a  I'etude  de  la  toxicite  de  la  phenacetine.  Ann  soc. 
de  med.  de  Gaud.,  1905,  85:  199. 

The  ingestion  of  15  grains  of  phenacetin  every  two  hours  for  twenty-four 
hours  was  followed  by  great  weakness  and  then  symptoms  of  collapse, 
with  tendency  to  syncope,  vertigo,  dyspnea,  cyanosis  of  the  extremities, 
precordial  pain,  nausea,  and  rapid  and  feeble  pulse.  The  skin  was  of  a 
yellowish-gray  color,  and  on  the  next  day  there  appeared  a  macular 
erythema.     Recovery  after  five  days. 

10()7. 

ToBEV.  rjEORfjE  L.  Fatal  i)oisoiiing  by  pjienacetin  in  headache  tablets.  Monthly 
Bulletin  of  the  State  Board  of  Health  of  .Massachusetts,  January.  lOOS. 

On  Friday.  December  13.  1907.  at  0.20  j).  m.,  a  girl  of  16.5  years,  in  good 
general  health,  but  having  a  headache  and  feeling  that  she  had  taken  cold, 
tr)ok  2  headache  tablets  and  went  to  bed.  Later,  her  mother  heard  her 
coughing  and  went  to  her.  There  was  nothing  at  this  time  to  cause  alarm, 
but  a  little  before  11  o'clock  the  girl's  lips  and  face  began  to  become  blue, 
and  in  consef^uence  a  physician  was  sent  for.  He  resi)onded  at  once,  and 
found  the  girl  with  great  weakness  of  the  heart  and  edema  of  the  lungs. 
Before  he  could  administer  any  remedy  she  was  dead. 

'I'he  box  with  tin;  remaining  tablets  was  sent  to  the  olfice  of  the  state 
board  of  health  fr)r  examination.  The  tablets  were  found  to  contain 
phenacetin.    The  box  was  labeled  "  Daubury's  Headache  Tablets." 


o 


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The  harmful  effects  of  acetanilid 
antipyrm,  and  phenacetin. 


1 


W  19  1955   C,U. 


Jil 


